MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Journal of Immunology' source. Wed, 08 Feb 2012 06:42:58 +0100 http://www.medworm.com/index.php?rid=5659827&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22301545%26dopt%3DAbstract Authors: Kerzerho J, Yu ED, Barra CM, Alari-Pahisa E, Girardi E, Harrak Y, Lauzurica P, Llebaria A, Zajonc DM, Akbari O, Castaño AR Abstract Activation of type I NKT (iNKT) cells by CD1d-presented agonists is a potent immunotherapeutic tool. α-Galactosylceramide (α-GalCer) is the prototypic agonist, but its excessive potency with simultaneous production of both pro- and anti-inflammatory cytokines hampers its potential therapeutic use. In search for novel agonists, we have analyzed the structure and function of HS44, a synthetic aminocyclitolic ceramide analog designed to avoid unrestrained iNKT cell activation. HS44 is a weaker agonist compared with α-GalCer in vitro, although in vivo it induces robust IFN-γ production, and highly reduced but still functional Th2 response. Th... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5659827 Wed, 01 Feb 2012 05:00:00 +0100 5659827 http://www.medworm.com/index.php?rid=5659826&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22301546%26dopt%3DAbstract Authors: Randall CM, Jokela JA, Shisler JL Abstract Molluscum contagiosum virus (MCV) causes persistent neoplasms in healthy and immunocompromised people. Its ability to persist likely is due to its arsenal of viral immunoevasion proteins. For example, the MCV MC159 protein inhibits TNF-R1-induced NF-κB activation and apoptosis. The MC159 protein is a viral FLIP and, as such, possesses two tandem death effector domains (DEDs). We show in this article that, in human embryonic kidney 293 T cells, the expression of wild-type MC159 or a mutant MC159 protein containing the first DED (MC159 A) inhibited TNF-induced NF-κB, or NF-κB activated by PMA or MyD88 overexpression, whereas a mutant protein lacking the first DED (MC159 B) did not. We hypothesized that the MC159 protein targeted ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5659826 Wed, 01 Feb 2012 05:00:00 +0100 5659826 http://www.medworm.com/index.php?rid=5659825&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22301547%26dopt%3DAbstract In this study, we demonstrate that HER2/HER3 signaling regulates the expression of MHC class I-related chain A and B (MICA and MICB) in breast cancer cell lines. The MICA and MICB (MICA/B) molecules act as key ligands for the activating receptor NK group 2, member D (NKG2D) and promote NK cell-mediated recognition and cytolysis. Genetic silencing of HER3 but not HER2 downregulated the expression of MICA/B, and HER3 overexpression significantly enhanced MICA expression. Among the major pathways activated by HER2/HER3 signaling, the PI3K/AKT pathway was shown to predominantly regulate MICA/B expression. Treatment with the HER3-specific ligand neuregulin 1β promoted the expression in a process that was antagonized by pharmacological and genetic interference with HER3 but not by the ataxia-te... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5659825 Wed, 01 Feb 2012 05:00:00 +0100 5659825 http://www.medworm.com/index.php?rid=5659824&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22301548%26dopt%3DAbstract In conclusion, this study identified the upregulation of MKP-1 by vitamin D as a novel pathway by which vitamin D inhibits LPS-induced p38 activation and cytokine production in monocytes/macrophages. PMID: 22301548 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5659824 Wed, 01 Feb 2012 05:00:00 +0100 5659824 http://www.medworm.com/index.php?rid=5642529&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22279102%26dopt%3DAbstract We report in this study that Gsr-null mice exhibited enhanced susceptibility to Escherichia coli challenge, indicated by dramatically increased bacterial burden, cytokine storm, striking histological abnormalities, and substantially elevated mortality. Additionally, Gsr-null mice exhibited elevated sensitivity to Staphylococcus aureus. Examination of the bactericidal functions of the neutrophils from Gsr-deficient mice in vitro revealed impaired phagocytosis and defective bacterial killing activities. Although Gsr catalyzes the regeneration of glutathione, a major cellular antioxidant, Gsr-deficient neutrophils paradoxically produced far less reactive oxygen species upon activation both ex vivo and in vivo. Unlike wild-type neutrophils that exhibited a sustained oxidative burst upon stimul... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5642529 Wed, 25 Jan 2012 05:00:00 +0100 5642529 http://www.medworm.com/index.php?rid=5642528&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22279103%26dopt%3DAbstract In conclusion, CD163-L1 exhibits similarity to CD163 in terms of structure and regulated expression in cultured monocytes but shows clear differences compared with the known CD163 ligand preferences and expression pattern in the pool of tissue macrophages. We postulate that CD163-L1 functions as a scavenger receptor for one or several ligands that might have a role in resolution of inflammation. PMID: 22279103 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5642528 Wed, 25 Jan 2012 05:00:00 +0100 5642528 http://www.medworm.com/index.php?rid=5642523&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22279104%26dopt%3DAbstract In this study we used confocal intravital microscopy in wild-type and Foxp3-GFP mice to examine adhesion of effector T cells and Tregs in dermal venules. These experiments examined a two-challenge model of contact sensitivity (CS) in which Treg abundance in the skin progressively increases during the course of the response. Adhesion of CD4(+) T cells increased during CS, peaking 8-24 h after an initial hapten challenge, and within 4 h of a second challenge. At these time points, 40% of adherent CD4(+) T cells were Foxp3(+) Tregs. CD4(+) T cell adhesion was highly dependent on ICAM-1, and consistent with this finding, anti-ICAM-1 prevented Treg adhesion. Skin TGF-β levels were elevated in skin during both challenges, in parallel with Treg adhesion. In the two-challenge CS model, inhibition... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5642523 Wed, 25 Jan 2012 05:00:00 +0100 5642523 http://www.medworm.com/index.php?rid=5642522&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22279105%26dopt%3DAbstract Authors: Obata Y, Takahashi D, Ebisawa M, Kakiguchi K, Yonemura S, Jinnohara T, Kanaya T, Fujimura Y, Ohmae M, Hase K, Ohno H Abstract Intestinal epithelial cells (IECs) have important functions as the first line of defense against diverse microorganisms on the luminal surface. Impaired integrity of IEC has been implicated in increasing the risk for inflammatory disorders in the gut. Notch signaling plays a critical role in the maintenance of epithelial integrity by regulating the balance of secretory and absorptive cell lineages, and also by facilitating epithelial cell proliferation. We show in this article that mice harboring IEC-specific deletion of Rbpj (RBP-J(ΔIEC)), a transcription factor that mediates signaling through Notch receptors, spontaneously develop chronic colitis... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5642522 Wed, 25 Jan 2012 05:00:00 +0100 5642522 http://www.medworm.com/index.php?rid=5642521&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22279106%26dopt%3DAbstract Authors: Hodawadekar S, Park K, Farrar MA, Atchison ML Abstract Stage-specific rearrangement of Ig H and L chain genes poses an enigma because both processes use the same recombinatorial machinery, but the H chain locus is accessible at the pro-B cell stage, whereas the L chain loci become accessible at the pre-B cell stage. Transcription factor STAT5 is a positive-acting factor for rearrangement of distal V(H) genes, but attenuation of IL-7 signaling and loss of activated STAT5 at the pre-B cell stage corresponds with Igκ locus accessibility and rearrangement, suggesting that STAT5 plays an inhibitory role at this locus. Indeed, loss of IL-7 signaling correlates with increased activity at the Igκ intron enhancer. However, the κE3' enhancer must also be regulated as this enhance... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5642521 Wed, 25 Jan 2012 05:00:00 +0100 5642521 http://www.medworm.com/index.php?rid=5642520&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22279107%26dopt%3DAbstract Authors: Anderson AC, Chandwaskar R, Lee DH, Sullivan JM, Solomon A, Rodriguez-Manzanet R, Greve B, Sobel RA, Kuchroo VK Abstract Experimental autoimmune encephalomyelitis (EAE) is a widely used model of multiple sclerosis. In NOD mice, EAE develops as a relapsing-remitting disease that transitions to a chronic progressive disease, making the NOD model the only mouse model that recapitulates the full clinical disease course observed in most multiple sclerosis patients. We have generated a TCR transgenic mouse that expresses the α- and β-chains of a myelin oligodendrocyte glycoprotein (MOG) 35-55-reactive TCR (1C6) on the NOD background. 1C6 TCR transgenic mice spontaneously generate both CD4(+) and CD8(+) T cells that recognize MOG and produce proinflammatory cytokines, allowing ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5642520 Wed, 25 Jan 2012 05:00:00 +0100 5642520 http://www.medworm.com/index.php?rid=5642519&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22279108%26dopt%3DAbstract In this study, we determined the causal relationship between nicotine-induced DC alterations and host response to vaccines. We show that animals exposed to nicotine failed to develop and maintain Ag-specific effector memory Th1 cells and Ab production to protein-based vaccine formulated with Th1 adjuvants. Accordingly, both prophylactic and therapeutic vaccines failed to protect and cure the nicotine-exposed mice from disease. More importantly, we demonstrate the nicotine-induced defects in the biological activities of in vivo DCs as an underlying mechanism. Indeed, i.v. administration of DCs differentiated in the presence of nicotine preferentially promoted the development of Ag-specific IL-4-producing effector cells in the challenged mice. In addition, DC subsets isolated from mice expos... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5642519 Wed, 25 Jan 2012 05:00:00 +0100 5642519 http://www.medworm.com/index.php?rid=5624571&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266279%26dopt%3DAbstract Authors: Kuckleburg CJ, Tilkens SM, Santoso S, Newman PJ Abstract Neutrophil transmigration requires the localization of neutrophils to endothelial cell junctions, in which receptor-ligand interactions and the action of serine proteases promote leukocyte diapedesis. NB1 (CD177) is a neutrophil-expressed surface molecule that has been reported to bind proteinase 3 (PR3), a serine protease released from activated neutrophils. PR3 has demonstrated proteolytic activity on a number of substrates, including extracellular matrix proteins, although its role in neutrophil transmigration is unknown. Recently, NB1 has been shown to be a heterophilic binding partner for the endothelial cell junctional protein, PECAM-1. Disrupting the interaction between NB1 and PECAM-1 significantly inhibits n... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624571 Fri, 20 Jan 2012 05:00:00 +0100 5624571 http://www.medworm.com/index.php?rid=5624570&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266280%26dopt%3DAbstract In this study, we investigated the underlying mechanism of Ets-1-mediated Il10 gene repression in Th1 cells. Compared with wild type Th1 cells, Ets-1 knockout Th1 cells expressed a significantly higher level of IL-10, which is comparable with that of wild type Th2 cells. Upregulation of IL-10 expression in Ets-1 knockout Th1 cells was accompanied by enhanced chromatin accessibility and increased recruitment of histone H3 acetylation at the Il10 regulatory regions. Reciprocally, Ets-1 deficiency significantly decreased histone deacetylase 1 (HDAC1) enrichment at the Il10 regulatory regions. Treatment with trichostatin A, an inhibitor of HDAC family, significantly increased Il10 gene expression by increasing histone H3 acetylation recruitment. We further demonstrated a physical interaction b... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624570 Fri, 20 Jan 2012 05:00:00 +0100 5624570 http://www.medworm.com/index.php?rid=5624569&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266281%26dopt%3DAbstract Authors: Wythe SE, Dodd JS, Openshaw PJ, Schwarze J Abstract CD4 Th differentiation is influenced by costimulatory molecules expressed on conventional dendritic cells (DCs) in regional lymph nodes and results in specific patterns of cytokine production. However, the function of costimulatory molecules on inflammatory (CD11b(+)) DCs in the lung during recall responses is not fully understood, but it is important for development of novel interventions to limit immunopathological responses to infection. Using a mouse model in which vaccination with vaccinia virus vectors expressing the respiratory syncytial virus (RSV) fusion protein (rVVF) or attachment protein (rVVG) leads to type 1- or type 2-biased cytokine responses, respectively, upon RSV challenge, we found expression of CD40 a... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624569 Fri, 20 Jan 2012 05:00:00 +0100 5624569 http://www.medworm.com/index.php?rid=5624568&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266282%26dopt%3DAbstract In this study, we investigated a model of intestinal inflammation driven by the intracellular apicomplexan parasite Eimeria falciformis. Although IFN-γ was the predominant cytokine during E. falciformis infection in wild-type mice, it was found to be dispensable for host defense and the development of intestinal inflammation. E. falciformis-infected IFN-γR(-/-) and IFN-γ(-/-) mice developed dramatically exacerbated body weight loss and intestinal pathology, but they surprisingly harbored fewer parasites. This was associated with a striking increase in parasite-specific IL-17A and IL-22 production in the mesenteric lymph nodes and intestine. CD4(+) T cells were found to be the source of IL-17A and IL-22, which drove the recruitment of neutrophils and increased tissue expression of anti-m... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624568 Fri, 20 Jan 2012 05:00:00 +0100 5624568 http://www.medworm.com/index.php?rid=5624567&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266283%26dopt%3DAbstract Authors: Khan T, Salunke DM Abstract The mechanistic basis for efficient combating of the infinite range of foreign Ags by the limited repertoire of naive Abs expressed on primary B cell surfaces during their first encounter was addressed through elegantly designed crystallographic analyses. Resolution of the discrepancy arising from the limited number of possible germline Ab receptors on primary B cells for recognizing the unlimited pool of possible Ags has been attempted by invoking the degenerate recognition potential of the germline Abs. Structural analyses of germline mAb BBE6.12H3 in an Ag-free state, as well as bound to four different peptide Ags, established the correlation of its degenerate specificity with conformational versatility of the paratope. Six distinct paratope ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624567 Fri, 20 Jan 2012 05:00:00 +0100 5624567 http://www.medworm.com/index.php?rid=5604039&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250079%26dopt%3DAbstract Authors: Sawaguchi M, Tanaka S, Nakatani Y, Harada Y, Mukai K, Matsunaga Y, Ishiwata K, Oboki K, Kambayashi T, Watanabe N, Karasuyama H, Nakae S, Inoue H, Kubo M Abstract We established a diphtheria toxin (DT)-based conditional deletion system using Il4 enhancer elements previously shown to be specific for IL-4 production in mast cells (MCs) or basophils (Mas-TRECK and Bas-TRECK mice). DT treatment of Bas-TRECK mice resulted in specific deletion of basophils, whereas both MCs and basophils were deleted in Mas-TRECK mice. DT-treated Mas-TRECK mice had impaired passive cutaneous anaphylaxis, IgE-mediated passive systemic anaphylaxis, and IgE-mediated chronic allergic inflammation, whereas DT-treated Bas-TRECK mice had impaired IgE-mediated chronic allergic inflammation. Using these m... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5604039 Mon, 16 Jan 2012 05:00:00 +0100 5604039 http://www.medworm.com/index.php?rid=5604007&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250080%26dopt%3DAbstract In this study, a novel heterozygous C3 mutation was identified in a factor B-binding region in exon 41, V1636A (4973 T > C). The mutation was found in three family members affected with late-onset atypical hemolytic uremic syndrome and symptoms of glomerulonephritis. All three patients exhibited increased complement activation detected by decreased C3 levels and glomerular C3 deposits. Platelets from two of the patients had C3 and C9 deposits on the cell surface. Patient sera exhibited more C3 cleavage and higher levels of C3a. The C3 mutation resulted in increased C3 binding to factor B and increased net formation of the C3 convertase, even after decay induced by decay-accelerating factor and factor H, as assayed by surface plasmon resonance. Patient sera incubated with washed human pl... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5604007 Mon, 16 Jan 2012 05:00:00 +0100 5604007 http://www.medworm.com/index.php?rid=5604006&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250081%26dopt%3DAbstract We describe an efficient way to generate B cells with strong suppressive functions by incubating naive B cells with a relevant Ag conjugated to cholera toxin B subunit (CTB). This allows most B cells, irrespective of BCR, to take up and present Ag and induces their expression of latency-associated polypeptide (LAP)/TGF-β and after adoptive transfer also their production of IL-10. With OVA as model Ag, when naive T cells were cocultured in vitro with B cells pretreated with OVA conjugated to CTB (OVA/CTB) Ag-specific CD4(+) Foxp3 regulatory T (Treg) cells increased >50-fold. These cells effectively suppressed CD25(-)CD4(+) effector T (Teff) cells in secondary cultures. Adoptive transfer of OVA/CTB-treated B cells to mice subsequently immunized with OVA in CFA induced increase in Foxp3 T... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5604006 Mon, 16 Jan 2012 05:00:00 +0100 5604006 http://www.medworm.com/index.php?rid=5604005&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250082%26dopt%3DAbstract Authors: Kinugawa S, Koide M, Kobayashi Y, Mizoguchi T, Ninomiya T, Muto A, Kawahara I, Nakamura M, Yasuda H, Takahashi N, Udagawa N Abstract Tetracyclines, such as doxycycline and minocycline, are used to suppress the growth of bacteria in patients with inflammatory diseases. Tetracyclines have been shown to prevent bone loss, but the mechanism involved is unknown. Osteoclasts and dendritic cells (DCs) are derived from common progenitors, such as bone marrow-derived macrophages (BMMs). In this article, we show that tetracyclines convert the differentiation pathway, resulting in DC-like cells not osteoclasts. Doxycycline and minocycline inhibited the receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis of BMMs, but they had no effects on cell growth and phagocytic... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5604005 Mon, 16 Jan 2012 05:00:00 +0100 5604005 http://www.medworm.com/index.php?rid=5604004&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250083%26dopt%3DAbstract This study analyzes the role of IL-21 on human in vivo-generated PC. IL-21R was clearly expressed on PC from the human tonsil, the lymph node, and the spleen (secondary lymphoid organs [SLO]) but barely on terminally mature bone marrow PC. IL-21 enhanced Ig secretion by isolated SLO PC but not bone marrow PC. Tonsillar T follicular helper (Tfh) lymphocytes are known to secrete IL-21. Purified Tfh cells induced a marked increase of Ig production by tonsillar PC, and this effect was impaired when endogenous IL-21 production was blocked. IL-21 provoked a rapid and transient phosphorylation of STAT3 in tonsillar PC. Tfh cells or exogenous IL-21 reduce tonsillar PC apoptosis and increases PC recovery but does not modify their nonproliferating status. These results suggest that IL-21 derived fro... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5604004 Mon, 16 Jan 2012 05:00:00 +0100 5604004 http://www.medworm.com/index.php?rid=5604003&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250084%26dopt%3DAbstract In conclusion, epidermal growth factor receptor tyrosine phosphorylates MUC1, leading to an increase in its association with TLR5, thereby competitively and reversibly inhibiting recruitment of MyD88 to TLR5 and downstream signaling events. This unique ability of MUC1 to control TLR5 signaling suggests its potential role in the pathogenesis of chronic inflammatory lung diseases. PMID: 22250084 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5604003 Mon, 16 Jan 2012 05:00:00 +0100 5604003 http://www.medworm.com/index.php?rid=5604002&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250085%26dopt%3DAbstract Authors: Sun Y, Karmakar M, Taylor PR, Rietsch A, Pearlman E Abstract Pseudomonas aeruginosa is a leading cause of blinding corneal ulcers worldwide. To determine the role of type III secretion in the pathogenesis of P. aeruginosa keratitis, corneas of C57BL/6 mice were infected with P. aeruginosa strain PAO1 or PAK, which expresses ExoS, ExoT, and ExoY, but not ExoU. PAO1- and PAK-infected corneas developed severe disease with pronounced opacification and rapid bacterial growth. In contrast, corneas infected with pscD or pscJ mutants that cannot assemble a type III secretion system, or with mutants lacking the translocator proteins, do not develop clinical disease, and bacteria are rapidly killed by infiltrating neutrophils. Furthermore, survival of PAO1 and PAK strains in the cor... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5604002 Mon, 16 Jan 2012 05:00:00 +0100 5604002 http://www.medworm.com/index.php?rid=5604001&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250086%26dopt%3DAbstract Authors: Costa A, Gupta R, Signorino G, Malara A, Cardile F, Biondo C, Midiri A, Galbo R, Trieu-Cuot P, Papasergi S, Teti G, Henneke P, Mancuso G, Golenbock DT, Beninati C Abstract Group B Streptococcus (GBS) is a frequent agent of life-threatening sepsis and meningitis in neonates and adults with predisposing conditions. We tested the hypothesis that activation of the inflammasome, an inflammatory signaling complex, is involved in host defenses against this pathogen. We show in this study that murine bone marrow-derived conventional dendritic cells responded to GBS by secreting IL-1β and IL-18. IL-1β release required both pro-IL-1β transcription and caspase-1-dependent proteolytic cleavage of intracellular pro-IL-1β. Dendritic cells lacking the TLR adaptor MyD88, but not those... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5604001 Mon, 16 Jan 2012 05:00:00 +0100 5604001 http://www.medworm.com/index.php?rid=5604000&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250087%26dopt%3DAbstract We examined the contribution of cytotoxic function to the therapeutic effect of allergen-specific CTL in allergic airway inflammation. We used a murine model of allergic airway inflammation in which mice were sensitized to OVA and then challenged with the same Ag via the intranasal route. CTL were elicited in these mice by immunization with dendritic cells (DC) or by adoptive transfer of in vitro-activated CD8(+) T cells. Hallmark features of allergic asthma, such as infiltration of eosinophils in the bronchoalveolar lavage fluid and mucus production, were assessed. Suppression of allergic airway inflammation by allergen-specific CTL was critically dependent on the expression of perforin, a key component of the cytotoxic machinery. Both perforin-sufficient and perforin-deficient allergen-s... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5604000 Mon, 16 Jan 2012 05:00:00 +0100 5604000 http://www.medworm.com/index.php?rid=5603999&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250088%26dopt%3DAbstract Authors: Rockwell CE, Zhang M, Fields PE, Klaassen CD Abstract NF erythroid 2-related factor 2 (Nrf2) is a transcription factor that mediates the upregulation of a battery of cytoprotective genes in response to cell stress. Recent studies showed that Nrf2 also modulates immune responses and exhibits anti-inflammatory activity. In this article, we demonstrate that a common food preservative, tert-butylhydroquinone, can activate Nrf2 in T cells, as evidenced by Nrf2 binding to the antioxidant response element and the subsequent upregulation of Nrf2 target genes. The activation of Nrf2 suppresses IFN-γ production, while inducing the production of the Th2 cytokines IL-4, IL-5, and IL-13. Nrf2 activation also suppresses T-bet DNA binding and promotes GATA-binding protein 3 DNA binding.... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5603999 Mon, 16 Jan 2012 05:00:00 +0100 5603999 http://www.medworm.com/index.php?rid=5603998&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250089%26dopt%3DAbstract Authors: Gardès P, Forveille M, Alyanakian MA, Aucouturier P, Ilencikova D, Leroux D, Rahner N, Mazerolles F, Fischer A, Kracker S, Durandy A Abstract Ig class-switch recombination (Ig-CSR) deficiencies are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect, defective Ig-CSR may also be associated with impaired somatic hypermutation (SHM) of the Ig V regions. Although the mechanisms underlying Ig-CSR and SHM in humans have been revealed (at least in part) by studying natural mutants, the role of mismatch repair in this process has not been fully elucidated. We studied in vivo and in vitro Ab maturation in eight MSH6-deficient patients. The skewed SHM pattern strongly suggests that MSH6 is involved... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5603998 Mon, 16 Jan 2012 05:00:00 +0100 5603998 http://www.medworm.com/index.php?rid=5603997&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250090%26dopt%3DAbstract Authors: Himoudi N, Morgenstern DA, Yan M, Vernay B, Saraiva L, Wu Y, Cohen CJ, Gustafsson K, Anderson J Abstract Activated human blood γδ T cells have also been previously demonstrated to behave as professional APCs, although the processes that control APC function have not been characterized. n this study, we show that the acquisition of potent APC function by human blood γδ T cells is achieved after physical interaction with an Ab-coated target cell, a process that we refer to as licensing. In cancer models, licensing of γδ T cells by tumor-reactive mAbs promotes the uptake of tumor Ags and professional presentation to tumor-reactive αβ T cells. We propose that licensing by Ab is a mechanism whereby the adaptive properties of γδ T cells are induced by their innate func... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5603997 Mon, 16 Jan 2012 05:00:00 +0100 5603997 http://www.medworm.com/index.php?rid=5603996&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250091%26dopt%3DAbstract In this study, we extend this principle to a strong synergism between the dectin-1 agonist curdlan and an inflammatory growth factor, GM-CSF. Both together act in synergy in inducing a strong inflammatory signature that converts immature dendritic cells (DCs) to potent effector DCs. A variety of cytokines (IL-1β, IL-6, TNF-α, IL-2, and IL-12p70), costimulatory molecules (CD80, CD86, CD40, and CD70), chemokines (CXCL1, CXCL2, CXCL3, CCL12, CCL17), as well as receptors and molecules involved in fugal recognition and immunity such as Mincle, dectin-1, dectin-2, and pentraxin 3 are strongly upregulated in DC treated simultaneously with curdlan and GM-CSF. The synergistic effect of both stimuli resulted in strong IκBα phosphorylation, its rapid degradation, and enhanced nuclear translocatio... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5603996 Mon, 16 Jan 2012 05:00:00 +0100 5603996 http://www.medworm.com/index.php?rid=5603995&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250092%26dopt%3DAbstract Authors: Radulovic K, Manta C, Rossini V, Holzmann K, Kestler HA, Wegenka UM, Nakayama T, Niess JH Abstract CD69 is highly expressed by lymphocytes at mucosal surfaces. We aimed to investigate the role of CD69 in mucosal immune responses. The expression of CD69 by CD4 T cells isolated from the spleen, mesenteric lymph nodes, small intestinal lamina propria, and colonic lamina propria was determined in specific pathogen-free B6 and TCR transgenic animals, as well as in germ-free B6 mice. Transfer colitis was induced by transplanting RAG(-/-) mice with B6 or CD69(-/-)CD45RB(high) CD4 T cells. CD69 expression by CD4 T cells is induced by the intestinal microflora, oral delivery of specific Ag, and type I IFN (IFN-I) signals. CD4 T cells from CD69(-/-) animals produce higher amounts of... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5603995 Mon, 16 Jan 2012 05:00:00 +0100 5603995 http://www.medworm.com/index.php?rid=5603994&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250093%26dopt%3DAbstract Authors: Veerman KM, Carlow DA, Shanina I, Priatel JJ, Horwitz MS, Ziltener HJ Abstract P-selectin glycoprotein ligand-1 (PSGL-1), a heavily glycosylated sialomucin expressed on most leukocytes, has dual function as a selectin ligand for leukocyte rolling on vascular selectins expressed in inflammation and as a facilitator of resting T cell homing into lymphoid organs. In this article, we document disturbances in T cell homeostasis present in PSGL-1(null) mice. Naive CD4(+) and CD8(+) T cell frequencies were profoundly reduced in blood, whereas T cell numbers in lymph nodes and spleen were at or near normal levels. Although PSGL-1(null) T cells were less efficient at entering lymph nodes, they also remained in lymph nodes longer than PSGL-1(+/+) T cells, suggesting that PSGL-1 supp... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5603994 Mon, 16 Jan 2012 05:00:00 +0100 5603994 http://www.medworm.com/index.php?rid=5561811&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210907%26dopt%3DAbstract Authors: Hansmann L, Schmidl C, Kett J, Steger L, Andreesen R, Hoffmann P, Rehli M, Edinger M Abstract CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) are pivotal for peripheral self-tolerance. They prevent immune responses to auto- and alloantigens and are thus under close scrutiny as cellular therapeutics for autoimmune diseases and the prevention or treatment of alloresponses after organ or stem cell transplantation. We previously showed that human Treg with a memory cell phenotype, but not those with a naive phenotype, rapidly downregulate expression of the lineage-defining transcription factor FOXP3 upon in vitro expansion. We now compared the transcriptomes of stable FOXP3(+) Treg and converted FOXP3(-) ex-Treg by applying a newly developed intranuclear staining protocol that... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561811 Fri, 30 Dec 2011 05:00:00 +0100 5561811 http://www.medworm.com/index.php?rid=5561810&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210908%26dopt%3DAbstract In this study, we show that nano-APC with engineered HLA alleles and IL-2 deliver peptide-MHC complexes, costimulatory molecules, and IL-2 to Ag-responding T cells, resulting in enhanced expression of CD25 and activation of TCR signaling pathways, while suppressing PD-1 expression on viral-responding CD8 T cells from chronic hepatitis B virus patients. The enhanced activation of CD4 and CD8 T cells induced by IL-2-nano-APC was Ag dependent and IL-2-nano-APC did not affect T regulatory cells. At a size of 500 nm, the nano-APC effectively induce immune synapse formation on Ag-specific T cells and accumulate as free particles in the lymphoid organs. These attributes of IL-2-nano-APC or other bioadjuvant-engineered nano-APC have profound implications for their use as a therapeutic strategy in ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561810 Fri, 30 Dec 2011 05:00:00 +0100 5561810 http://www.medworm.com/index.php?rid=5561809&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210909%26dopt%3DAbstract Authors: Frank GM, Buela KA, Maker DM, Harvey SA, Hendricks RL Abstract Dendritic cells (DCs) regulate both innate and adaptive immune responses. In this article, we exploit the unique avascularity of the cornea to examine a role for local or very early infiltrating DCs in regulating the migration of blood-derived innate immune cells toward HSV-1 lesions. A single systemic diphtheria toxin treatment 2 d before HSV-1 corneal infection transiently depleted CD11c(+) DCs from both the cornea and lymphoid organs of CD11c-DTR bone marrow chimeric mice for up to 24 h postinfection. Transient DC depletion significantly delayed HSV-1 clearance from the cornea through 6 d postinfection. No further compromise of viral clearance was observed when DCs were continuously depleted throughout the f... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561809 Fri, 30 Dec 2011 05:00:00 +0100 5561809 http://www.medworm.com/index.php?rid=5561808&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210910%26dopt%3DAbstract Authors: Giangreco A, Hoste E, Takai Y, Rosewell I, Watt FM Abstract Autoimmune alopecia is characterized by an extensive epidermal T cell infiltrate that mediates hair follicle destruction. We have investigated the role of cell adhesion molecule 1 (Cadm1; Necl2) in this disease. Cadm1 is expressed by epidermal cells and mediates heterotypic adhesion to lymphocytes expressing class 1-restricted T cell-associated molecule (CRTAM). Using a murine autoimmune alopecia model, we observed an increase in early-activated cytotoxic (CD8-restricted, CRTAM-expressing) T cells, which preferentially associated with hair follicle keratinocytes expressing Cadm1. Coculture with Cadm1-transduced MHC-matched APCs stimulated alopecic lymph node cells to release IL-2 and IFN-γ. Overexpression of Cadm... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561808 Fri, 30 Dec 2011 05:00:00 +0100 5561808 http://www.medworm.com/index.php?rid=5561807&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210911%26dopt%3DAbstract In this study, we extend our in vitro findings and determine that IL-13 increases IL-10 production from Th17-polarized cells and that IL-13-induced IL-10 production negatively regulates the secretion of IL-17A and IL-21. To determine if IL-13 negatively regulates lung IL-17A expression via an IL-10-dependent mechanism in vivo, we used a model of respiratory syncytial virus (RSV) strain A2 infection in STAT1 knockout (KO) mice that increases lung IL-17A and IL-13 expression, cytokines not produced during RSV infection in wild-type mice. To test the hypothesis that IL-13 negatively regulates lung IL-17A expression, we created STAT1/IL-13 double KO (DKO) mice. We found that RSV-infected STAT1/IL-13 DKO mice had significantly greater lung IL-17A expression compared with that of STAT1 KO mice a... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561807 Fri, 30 Dec 2011 05:00:00 +0100 5561807 http://www.medworm.com/index.php?rid=5561806&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210912%26dopt%3DAbstract Authors: Ioannou M, Alissafi T, Lazaridis I, Deraos G, Matsoukas J, Gravanis A, Mastorodemos V, Plaitakis A, Sharpe A, Boumpas D, Verginis P Abstract There is a need in autoimmune diseases to uncover the mechanisms involved in the natural resolution of inflammation. In this article, we demonstrate that granulocytic myeloid-derived suppressor cells (G-MDSCs) abundantly accumulate within the peripheral lymphoid compartments and target organs of mice with experimental autoimmune encephalomyelitis prior to disease remission. In vivo transfer of G-MDSCs ameliorated experimental autoimmune encephalomyelitis, significantly decreased demyelination, and delayed disease onset through inhibition of encephalitogenic Th1 and Th17 immune responses. Exposure of G-MDSCs to the autoimmune milieu le... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561806 Fri, 30 Dec 2011 05:00:00 +0100 5561806 http://www.medworm.com/index.php?rid=5561805&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210913%26dopt%3DAbstract Authors: Hess E, Duheron V, Decossas M, Lézot F, Berdal A, Chea S, Golub R, Bosisio MR, Bridal SL, Choi Y, Yagita H, Mueller CG Abstract RANK and its ligand RANKL play important roles in the development and regulation of the immune system. We show that mice transgenic for Rank in hair follicles display massive postnatal growth of skin-draining lymph nodes. The proportions of hematopoietic and nonhematopoietic stromal cells and their organization are maintained, with the exception of an increase in B cell follicles. The hematopoietic cells are not activated and respond to immunization by foreign Ag and adjuvant. We demonstrate that soluble RANKL is overproduced from the transgenic hair follicles and that its neutralization normalizes lymph node size, inclusive area, and numbers of ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561805 Fri, 30 Dec 2011 05:00:00 +0100 5561805 http://www.medworm.com/index.php?rid=5561804&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210914%26dopt%3DAbstract Authors: Hemmi H, Zaidi N, Wang B, Matos I, Fiorese C, Lubkin A, Zbytnuik L, Suda K, Zhang K, Noda M, Kaisho T, Steinman RM, Idoyaga J Abstract Members of the triggering expressed on myeloid cells (Trem) receptor family fine-tune inflammatory responses. We previously identified one of these receptors, called Treml4, expressed mainly in the spleen, as well as at high levels by CD8α(+) dendritic cells and macrophages. Like other Trem family members, Treml4 has an Ig-like extracellular domain and a short cytoplasmic tail that associates with the adaptor DAP12. To follow up on our initial results that Treml4-Fc fusion proteins bind necrotic cells, we generated a knockout mouse to assess the role of Treml4 in the uptake and presentation of dying cells in vivo. Loss of Treml4 expression... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561804 Fri, 30 Dec 2011 05:00:00 +0100 5561804 http://www.medworm.com/index.php?rid=5561803&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210915%26dopt%3DAbstract In this study, we characterized the adhesion G-protein coupled receptor CD97, present on peripheral myeloid cells, as a novel interacting partner for Thy-1. CD97 was upregulated on polymorphonuclear cells (PMNC) of patients with psoriasis. In psoriatic skin lesions, CD97(+) myeloid cells colocalized with Thy-1(+) EC of small vessels in microabscesses, suggesting an interaction between CD97 and Thy-1 that was further examined by adhesion and protein-binding assays. PMNC and cell lines stably overexpressing CD97 adhered specifically to Thy-1(+)-activated human dermal EC, Thy-1(+) CHO cells, and immobilized Thy-1 protein. Binding of the CD97(+) CHO clones correlated with their CD97 expression level. Soluble CD97 bound specifically to immobilized Thy-1 protein, as well as Thy-1(+)-activated EC... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561803 Fri, 30 Dec 2011 05:00:00 +0100 5561803 http://www.medworm.com/index.php?rid=5561802&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210916%26dopt%3DAbstract In this study, we conducted a longitudinal analysis of clonality, phenotype, and function to define the characteristics of HIV-specific CD8 T cell populations that persist under conditions of limited antigenic stimulation. Ag decay was associated with dynamic changes in the TCR repertoire, increased expression of CD45RA and CD127, decreased expression of programmed death-1, and the emergence of polyfunctional HIV-specific CD8 T cells. High-definition analysis of individual clonotypes revealed that the Ag loss-induced gain of function within HIV-specific CD8 T cell populations could be attributed to two nonexclusive mechanisms: 1) functional improvement of persisting clonotypes; and 2) recruitment of particular clonotypes endowed with superior functional capabilities. PMID: 22210916 [Pu... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561802 Fri, 30 Dec 2011 05:00:00 +0100 5561802 http://www.medworm.com/index.php?rid=5561801&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210917%26dopt%3DAbstract Authors: Fagundes CT, Amaral FA, Vieira AT, Soares AC, Pinho V, Nicoli JR, Vieira LQ, Teixeira MM, Souza DG Abstract Mammals are colonized by an astronomical number of commensal microorganisms on their environmental exposed surfaces. These symbiotic species build up a complex community that aids their hosts in several physiological activities. We have shown that lack of intestinal microbiota is accompanied by a state of active IL-10-mediated inflammatory hyporesponsiveness. The present study investigated whether the germfree state and its hyporesponsive phenotype alter host resistance to an infectious bacterial insult. Experiments performed in germfree mice infected with Klebsiella pneumoniae showed that these animals are drastically susceptible to bacterial infection in an IL-10-d... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561801 Fri, 30 Dec 2011 05:00:00 +0100 5561801 http://www.medworm.com/index.php?rid=5561800&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210918%26dopt%3DAbstract We examined signaling pathways involved in the HIV enhancing effect of TLR2. TLR2 but not IL-2 signals promoted HIV nuclear import; however, both signals were required for the maximal enhancing effect. Although TLR2 signaling could not activate T cells, it increased IL-2-induced T cell activation. Cyclosporin A and IkBα inhibitor blocked TLR2-mediated enhancement of HIV infection/nuclear import. PI3K inhibitor blocked HIV infection/nuclear import and T cell activation and exerted a moderate inhibitory effect on cell cycle progression in CD4(+) T cells activated by TLR2/IL-2. Blockade of p38 signaling suppressed TLR2-mediated enhancement of HIV nuclear import/infection. However, the p38 inhibitor did not have a significant effect on T cell activation or TCR/CD3-mediated enhancement of HIV ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561800 Fri, 30 Dec 2011 05:00:00 +0100 5561800 http://www.medworm.com/index.php?rid=5561799&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210919%26dopt%3DAbstract Authors: Bahaie NS, Hosseinkhani MR, Ge XN, Kang BN, Ha SG, Blumenthal MS, Jessberger R, Rao SP, Sriramarao P Abstract Eosinophils are the predominant inflammatory cells recruited to allergic airways. In this article, we show that human and murine eosinophils express SWAP-70, an intracellular RAC-binding signaling protein, and examine its role in mediating eosinophil trafficking and pulmonary recruitment in a murine model of allergic airway inflammation. Compared with wild-type eosinophils, SWAP-70-deficient (Swap-70(-/-)) eosinophils revealed altered adhesive interactions within inflamed postcapillary venules under conditions of blood flow by intravital microscopy, exhibiting enhanced slow rolling but decreased firm adhesion. In static adhesion assays, Swap-70(-/-) eosinophils adh... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5561799 Fri, 30 Dec 2011 05:00:00 +0100 5561799 http://www.medworm.com/index.php?rid=5550780&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198947%26dopt%3DAbstract In this study, we report that semaphorin 7A (Sema7A), a GPI-anchored semaphorin expressed in intestinal epithelial cells (IECs), induces IL-10 production by intestinal Mϕs to regulate intestinal inflammation. Sema7A-deficient mice showed severe signs of dextran sodium sulfate-induced colitis due to reduced intestinal IL-10 levels. We further identified CX3CR1(+)MHC class II(int)F4/80(hi)CD11b(hi) Mϕs as the main producers of IL-10 via αvβ1 integrin in response to Sema7A. Notably, Sema7A was predominantly expressed on the basolateral side of IECs, and its expression pattern was responsible for protective effects against dextran sodium sulfate-induced colitis and IL-10 production by Mϕs during interactions between IECs and Mϕs. Furthermore, we determined that the administration of reco... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5550780 Fri, 23 Dec 2011 05:00:00 +0100 5550780 http://www.medworm.com/index.php?rid=5550779&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198948%26dopt%3DAbstract Authors: Bartemes KR, Iijima K, Kobayashi T, Kephart GM, McKenzie AN, Kita H Abstract Innate immunity provides the first line of response to invading pathogens and a variety of environmental insults. Recent studies identified novel subsets of innate lymphoid cells that are capable of mediating immune responses in mucosal organs. In this paper, we describe a subset of lymphoid cells that is involved in innate type 2 immunity in the lungs. Airway exposure of naive BALB/c or C57BL/6J mice to IL-33 results in a rapid (<12 h) production of IL-5 and IL-13 and marked airway eosinophilia independently of adaptive immunity. In the lungs of nonsensitized naive mice, IL-33-responsive cells were identified that have a lymphoid morphology, lack lineage markers, highly express CD25, CD44, Thy... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5550779 Fri, 23 Dec 2011 05:00:00 +0100 5550779 http://www.medworm.com/index.php?rid=5550778&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198949%26dopt%3DAbstract In this study, we used real-time surface plasmon resonance spectroscopy and conventional biochemical pull-down assays to demonstrate a direct interaction between TLR2 and the aggregated 42-aa form of human Aβ (Aβ42). TLR2 deficiency reduced Aβ42-triggered inflammatory activation but enhanced Aβ phagocytosis in cultured microglia and macrophages. By expressing TLR2 in HEK293 cells that do not endogenously express TLR2, we observed that TLR2 expression enabled HEK293 cells to respond to Aβ42. Through site-directed mutagenesis of tlr2 gene, we identified the amino acids EKKA (741-744) as a critical cytoplasmic domain for transduction of inflammatory signals. By coexpressing TLR1 or TLR6 in TLR2-transgenic HEK293 cells or silencing tlrs genes in RAW264.7 macrophages, we observed that TLR2... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5550778 Fri, 23 Dec 2011 05:00:00 +0100 5550778 http://www.medworm.com/index.php?rid=5550777&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198950%26dopt%3DAbstract Authors: Elvington A, Atkinson C, Kulik L, Zhu H, Yu J, Kindy MS, Holers VM, Tomlinson S Abstract Self-reactive natural Abs initiate injury following ischemia and reperfusion of certain tissues, but their role in ischemic stroke is unknown. We investigated neoepitope expression in the postischemic brain and the role of natural Abs in recognizing these epitopes and mediating complement-dependent injury. A novel IgM mAb recognizing a subset of phospholipids (C2) and a previously characterized anti-annexin IV mAb (B4) were used to reconstitute and characterize injury in Ab-deficient Rag1(-/-) mice after 60 min of middle cerebral artery occlusion and reperfusion. Reconstitution with C2 or B4 mAb in otherwise protected Rag1(-/-) mice restored injury to that seen in wild-type (wt) mice, ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5550777 Fri, 23 Dec 2011 05:00:00 +0100 5550777 http://www.medworm.com/index.php?rid=5550776&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198951%26dopt%3DAbstract Authors: van der Heijden J, Breunis WB, Geissler J, de Boer M, van den Berg TK, Kuijpers TW Abstract The balance between activating and inhibitory signals from the different FcγRs for IgG ensures homeostasis of many inflammatory responses. FCGR2C is the product of an unequal crossover of the FCGR2A and FCGR2B genes encoding the activating FcγRIIa (CD32a) and inhibitory FcγRIIb (CD32b), respectively. A single nucleotide polymorphism (SNP) in exon 3 of FCGR2C results in either expression of the activating FcγRIIc (CD32c) (FCGR2C-open reading frame [ORF]) or its absence because of a stop codon (FCGR2C-Stop). Two additional variations in FcγRIIb/c expression on leukocytes have now been identified. In case of "nonclassical" FCGR2C-ORF alleles, FcγRIIc expression was unexpectedly a... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5550776 Fri, 23 Dec 2011 05:00:00 +0100 5550776 http://www.medworm.com/index.php?rid=5550775&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198952%26dopt%3DAbstract Authors: Maseda D, Smith SH, Dilillo DJ, Bryant JM, Candando KM, Weaver CT, Tedder TF Abstract Regulatory B cells that are functionally defined by their capacity to express IL-10 (B10 cells) downregulate inflammation and autoimmunity. In studies using well-defined IL-10 reporter mice, this rare B10 cell subset was also found to maintain a capacity for plasma cell differentiation. During a transient period of il10 transcription, the blimp1 and irf4 transcription factors were induced in B10 cells, whereas pax5 and bcl6 were downregulated as a significant fraction of B10 cells completed the genetic and phenotypic program leading to Ab-secreting cell differentiation in vitro and in vivo. B10 cell-derived IgM reacted with both self- and foreign Ags, whereas B10 cells generated Ag-specif... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5550775 Fri, 23 Dec 2011 05:00:00 +0100 5550775 http://www.medworm.com/index.php?rid=5550774&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198953%26dopt%3DAbstract In this study, we demonstrate Helios expression in Foxp3(+) iTreg, both in vitro and in vivo. Following i.v. peptide injection, in vivo Helios expression in adoptively transferred TCR transgenic T cells was more rapid than Foxp3 induction but less stable at later time points without a second injection of peptide. Our in vitro data suggest that APC influence Helios expression in a manner distinct from stimuli required for Foxp3 induction. Thus, Helios expression in iTreg may reflect the context of stimulation during Foxp3 induction. In summary, the robust Helios expression we observe in iTreg precludes its use as a marker of thymic Treg. PMID: 22198953 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5550774 Fri, 23 Dec 2011 05:00:00 +0100 5550774 http://www.medworm.com/index.php?rid=5550773&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198954%26dopt%3DAbstract Authors: Miloud T, Fiegler N, Suffner J, Hämmerling GJ, Garbi N Abstract Bone marrow-derived dendritic cell (DC) precursors seed peripheral organs, where they encounter diverse cellular environments during their final differentiation into DCs. Flt3 ligand (Flt3-L) is critical for instructing DC generation throughout different organs. However, it remains unknown which cells produce Flt3-L and, importantly, which cellular source drives DC development in such a variety of organs. Using a novel BAC transgenic Flt3-L reporter mouse strain coexpressing enhanced GFP and luciferase, we show ubiquitous Flt3-L expression in organs and cell types. These results were further confirmed at the protein level. Although Flt3-L was produced by immune and nonimmune cells, the source required for dev... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5550773 Fri, 23 Dec 2011 05:00:00 +0100 5550773 http://www.medworm.com/index.php?rid=5550772&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198955%26dopt%3DAbstract In this report, we examine the immune correlates of AC-RTA-mediated protection and show that sterilizing immunity requires both T cells and Ab. Importantly, Ab was also critical for mitigating viral infection in the brain, and in the absence of Ab-mediated control, amplification of the AC-RTA virus in the brain resulted in fatality. Our results highlight important considerations in the development of vaccination strategies based on live-attenuated viruses. PMID: 22198955 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5550772 Fri, 23 Dec 2011 05:00:00 +0100 5550772 http://www.medworm.com/index.php?rid=5536699&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190179%26dopt%3DAbstract Authors: Hardy CL, Lemasurier JS, Belz GT, Scalzo-Inguanti K, Yao J, Xiang SD, Kanellakis P, Bobik A, Strickland DH, Rolland JM, O'Hehir RE, Plebanski M Abstract Nanoparticles are being developed for diverse biomedical applications, but there is concern about their potential to promote inflammation, particularly in the lung. Although a variety of ambient, anthropogenic and man-made nanoparticles can promote lung inflammation, little is known about the long-term immunomodulatory effects of inert noninflammatory nanoparticles. We previously showed polystyrene 50-nm nanoparticles coated with the neutral amino acid glycine (PS50G nanoparticles) are not inflammatory and are taken up preferentially by dendritic cells (DCs) in the periphery. We tested the effects of such nanoparticles on ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5536699 Wed, 21 Dec 2011 05:00:00 +0100 5536699 http://www.medworm.com/index.php?rid=5536698&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190180%26dopt%3DAbstract We report two patients with a homozygous R429C point mutation in STIM1 completely abolishing store-operated calcium entry in T cells. Immunological analysis of one patient revealed that despite the expected defect of T cell proliferation and cytokine production in vitro, significant antiviral T cell populations were generated in vivo. These T cells proliferated in response to viral Ags and showed normal antiviral cytotoxicity. However, antiviral immunity was insufficient to prevent chronic CMV and EBV infections with a possible contribution of impaired NK cell function and a lack of NKT cells. Furthermore, autoimmune cytopenia, eczema, and intermittent diarrhea suggested impaired immune regulation. FOXP3-positive regulatory T (Treg) cells were present but showed an abnormal phenotype. The ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5536698 Wed, 21 Dec 2011 05:00:00 +0100 5536698 http://www.medworm.com/index.php?rid=5536697&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190181%26dopt%3DAbstract Authors: Holley MM, Kielian T Abstract Brain abscesses arise following parenchymal infection with pyogenic bacteria and are typified by inflammation and edema, which frequently results in a multitude of long-term health problems. The impact of adaptive immunity in shaping continued innate responses during late-stage brain abscess formation is not known but is important, because robust innate immunity is required for effective bacterial clearance. To address this issue, brain abscesses were induced in TCR αβ knockout (KO) mice, because CD4(+) and NKT cells represented the most numerous T cell infiltrates. TCR αβ KO mice exhibited impaired bacterial clearance during later stages of infection, which was associated with alterations in neutrophil and macrophage recruitment, as well ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5536697 Wed, 21 Dec 2011 05:00:00 +0100 5536697 http://www.medworm.com/index.php?rid=5536696&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190182%26dopt%3DAbstract Authors: Través PG, de Atauri P, Marín S, Pimentel-Santillana M, Rodríguez-Prados JC, Marín de Mas I, Selivanov VA, Martín-Sanz P, Boscá L, Cascante M Abstract The activation of immune cells in response to a pathogen involves a succession of signaling events leading to gene and protein expression, which requires metabolic changes to match the energy demands. The metabolic profile associated with the MAPK cascade (ERK1/2, p38, and JNK) in macrophages was studied, and the effect of its inhibition on the specific metabolic pattern of LPS stimulation was characterized. A [1,2-[(13)C](2)]glucose tracer-based metabolomic approach was used to examine the metabolic flux distribution in these cells after MEK/ERK inhibition. Bioinformatic tools were used to analyze changes in mass isot... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5536696 Wed, 21 Dec 2011 05:00:00 +0100 5536696 http://www.medworm.com/index.php?rid=5536695&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190183%26dopt%3DAbstract In conclusion, the nTreg population mirrors the effector T cell population in the frequency of Ag-reactive T cells. Isolation and expansion of functional Ag-reactive nTregs is possible and of potential benefit for specific therapeutic goals. PMID: 22190183 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5536695 Wed, 21 Dec 2011 05:00:00 +0100 5536695 http://www.medworm.com/index.php?rid=5536694&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190184%26dopt%3DAbstract Authors: Klein M, Vaeth M, Scheel T, Grabbe S, Baumgrass R, Berberich-Siebelt F, Bopp T, Schmitt E, Becker C Abstract The main molecular mechanism of human regulatory T cell (Treg)-mediated suppression has not been elucidated. We show in this study that cAMP represents a key regulator of human Treg function. Repression of cAMP production by inhibition of adenylate cyclase activity or augmentation of cAMP degradation through ectopic expression of a cAMP-degrading phosphodiesterase greatly reduces the suppressive activity of human Treg in vitro and in a humanized mouse model in vivo. Notably, cAMP repression additionally abrogates the anergic state of human Treg, accompanied by nuclear translocation of NFATc1 and induction of its short isoform NFATc1/αA. Treg expanded under cAMP rep... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5536694 Wed, 21 Dec 2011 05:00:00 +0100 5536694 http://www.medworm.com/index.php?rid=5536693&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190185%26dopt%3DAbstract In this study, tissue-specific eosinophil mRNA microarray analysis identified that CD22 transcript levels of murine gastrointestinal (GI) eosinophils are 10-fold higher than those of lung eosinophils. To confirm the mRNA data at the protein level, we developed a FACS-based protocol designed to phenotype live GI eosinophils isolated from the murine lamina propria. Indeed, we found that jejunum eosinophils expressed remarkably high levels of surface CD22, similar to levels found in B cells across multiple mouse strains. In contrast, CD22 was undetectable on eosinophils from the colon, blood, thymus, spleen, uterus, peritoneal cavity, and allergen-challenged lung. Eosinophils isolated from newborn mice did not express CD22 but subsequently upregulated CD22 expression to adult levels within th... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5536693 Wed, 21 Dec 2011 05:00:00 +0100 5536693 http://www.medworm.com/index.php?rid=5514615&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174445%26dopt%3DAbstract In this report, we describe the generation of an IL-5 reporter mouse and identify IL-5-producing non-T lymphoid cells that reside in the intestine, peritoneal cavity, and lungs in naive mice. They share many characteristics with natural helper cells, nuocytes, and Ih2 cells, including surface Ags and responsiveness to cytokines. However, these phenotypes do not completely overlap with any particular one of these cell types. Innate non-T IL-5-producing cells localized most abundantly in the lung and proliferated and upregulated IL-5 production in response to IL-25 and IL-33. IL-33 was more effective than IL-25. These cells contribute to maintaining sufficient numbers of lung eosinophils and are important for eosinophil recruitment mediated by IL-25 and IL-33. Given that eosinophils are show... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514615 Wed, 14 Dec 2011 05:00:00 +0100 5514615 http://www.medworm.com/index.php?rid=5514614&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174446%26dopt%3DAbstract Authors: Gordon SN, Kines RC, Kutsyna G, Ma ZM, Hryniewicz A, Roberts JN, Fenizia C, Hidajat R, Brocca-Cofano E, Cuburu N, Buck CB, Bernardo ML, Robert-Guroff M, Miller CJ, Graham BS, Lowy DR, Schiller JT, Franchini G Abstract The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T and B cells in the female genital tract may prevent the establishment and systemic dissemination of HIV. We tested the immunogenicity of a vaccine that uses human papillomavirus (HPV)-based gene transfer vectors, also called pseudovirions (PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514614 Wed, 14 Dec 2011 05:00:00 +0100 5514614 http://www.medworm.com/index.php?rid=5514613&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174447%26dopt%3DAbstract This study demonstrates that L. sigmodontis-mediated protection against diabetes in NOD mice is not dependent on the induction of a type 2 immune shift but does require TGF-β. PMID: 22174447 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514613 Wed, 14 Dec 2011 05:00:00 +0100 5514613 http://www.medworm.com/index.php?rid=5514612&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174448%26dopt%3DAbstract In this study, we demonstrate that human Ag-specific CD8(+) T cells acquire the coinhibitory molecule programmed death ligand 1 (PD-L1) from mature dendritic cells (mDC) and tumor cells in an Ag-specific manner. Immature dendritic cells were less effective in transferring surface molecules onto CD8(+) T cells than mDCs. Interestingly, trogocytosis of PD-L1 requires cell-cell contact and cannot be induced by uptake of soluble proteins obtained from mDC lysates. The transfer process is impaired by inhibition of vacuolar ATPases in T cells as well as by fixation of dendritic cells. Of importance, CD8(+) T cells that acquired PD-L1 complexes were able to induce apoptosis of neighboring programmed death 1-expressing CD8(+) T cells. In summary, our data demonstrate that human CD8(+) T cells take... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514612 Wed, 14 Dec 2011 05:00:00 +0100 5514612 http://www.medworm.com/index.php?rid=5514611&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174449%26dopt%3DAbstract Authors: Xia L, Tian D, Huang W, Zhu H, Wang J, Zhang Y, Hu H, Nie Y, Fan D, Wu K Abstract IL-23 is a newly discovered proinflammatory cytokine that contributes to the maintenance and expansion of Th17 cells. IL-23 has recently been identified as playing a critical role in a number of chronic inflammatory diseases. However, the regulatory mechanism of IL-23 in chronic hepatitis B (CHB) remains largely unknown. The aims of this study were to detect the expression of IL-23 in CHB patients and to explore the molecular mechanism of hepatitis B virus (HBV)-induced IL-23 expression. Serum levels and hepatic expression of IL-23 were significantly upregulated in CHB patients. A positive correlation was found between IL-23 expression and the histological activity index score, HBV DNA load, ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514611 Wed, 14 Dec 2011 05:00:00 +0100 5514611 http://www.medworm.com/index.php?rid=5514610&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174450%26dopt%3DAbstract Authors: Xue L, Barrow A, Fleming VM, Hunter MG, Ogg G, Klenerman P, Pettipher R Abstract PGD(2) exerts a number of proinflammatory responses through a high-affinity interaction with chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and has been detected at high concentrations at sites of allergic inflammation. Because cysteinyl leukotrienes (cysLTs) are also produced during the allergic response, we investigated the possibility that cysLTs may modulate the response of human Th2 cells to PGD(2). PGD(2) induced concentration-dependent Th2 cytokine production in the absence of TCR stimulation. Leukotrienes D(4) and E(4) (LTE(4)) also stimulated the cytokine production but were much less active than PGD(2). However, when combined with PGD(2), cysLTs caused a ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514610 Wed, 14 Dec 2011 05:00:00 +0100 5514610 http://www.medworm.com/index.php?rid=5514609&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174451%26dopt%3DAbstract Authors: Chockalingam A, Rose WA, Hasan M, Ju CH, Leifer CA Abstract Compartmentalization of nucleic acid sensing TLR9 has been implicated as a mechanism to prevent recognition of self nucleic acid structures. Furthermore, recognition of CpG DNA in different endosomal compartments leads to the production of the proinflammatory cytokine TNF-α, or type I IFN. We previously characterized a tyrosine-based motif at aa 888-891 in the cytoplasmic tail of TLR9 important for appropriate intracellular localization. In this article, we show that this motif is selectively required for the production of TNF, but not IFN. In response to CpG DNA stimulation, the proteolytically processed 80-kDa fragment is tyrosine phosphorylated. Although Y888 is not itself phosphorylated, the structure of this... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514609 Wed, 14 Dec 2011 05:00:00 +0100 5514609 http://www.medworm.com/index.php?rid=5514608&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174452%26dopt%3DAbstract Authors: Takeda K, Thurman JM, Tomlinson S, Okamoto M, Shiraishi Y, Ferreira VP, Cortes C, Pangburn MK, Holers VM, Gelfand EW Abstract Activation of the alternative pathway of complement plays a critical role in the development of allergen-induced airway hyperresponsiveness (AHR) and inflammation in mice. Endogenous factor H, a potent inhibitor of the alternative pathway, is increased in the airways of sensitized and challenged mice, but its role in regulating inflammation or AHR has been unknown. We found that blocking the tissue-binding function of factor H with a competitive antagonist increased complement activation and tissue inflammation after allergen challenge of sensitized mice. Conversely, administration of a fusion protein that contains the iC3b/C3d binding region of com... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514608 Wed, 14 Dec 2011 05:00:00 +0100 5514608 http://www.medworm.com/index.php?rid=5514607&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174453%26dopt%3DAbstract Authors: Sironi M, Biasin M, Cagliani R, Forni D, De Luca M, Saulle I, Lo Caputo S, Mazzotta F, Macías J, Pineda JA, Caruz A, Clerici M Abstract TLR3 recognizes dsRNA and activates antiviral immune responses through the production of inflammatory cytokines and type I IFNs. Genetic association studies have provided evidence concerning the role of a polymorphism in TLR3 (rs3775291, Leu412Phe) in viral infection susceptibility. We genotyped rs3775291 in a population of Spanish HIV-1-exposed seronegative (HESN) individuals who remain HIV seronegative despite repeated exposure through i.v. injection drug use (IDU-HESN individuals) as witnessed by their hepatitis C virus seropositivity. The frequency of individuals carrying at least one 412Phe allele was significantly higher in IDU-HESN... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514607 Wed, 14 Dec 2011 05:00:00 +0100 5514607 http://www.medworm.com/index.php?rid=5514606&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174454%26dopt%3DAbstract This study showed that influenza infection markedly increased the expression of multiple gene classes capable of sensing allergens and amplifying the ensuing immune-inflammatory response. We propose that influenza A infection primes the lung environment in such a way as to lower the threshold of allergen responsiveness, thus facilitating the emergence of a clinically significant allergic phenotype. PMID: 22174454 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514606 Wed, 14 Dec 2011 05:00:00 +0100 5514606 http://www.medworm.com/index.php?rid=5514605&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174455%26dopt%3DAbstract In this study we demonstrate that the UVR-inducible antimicrobial peptide murine β-defensin-14 (mBD-14) switches CD4(+)CD25(-) T cells into a regulatory phenotype by inducing the expression of specific markers like Foxp3 and CTLA-4. This is functionally relevant because mBD-14-treated T cells inhibit sensitization upon adoptive transfer into naive C57BL/6 mice. Accordingly, injection of mBD-14, comparable to UVR, suppresses the induction of contact hypersensitivity and induces Ag-specific regulatory T cells (Tregs). Further evidence for the ability of mBD-14 to induce Foxp3(+) T cells is provided using DEREG (depletion of Tregs) mice in which Foxp3-expressing cells can be depleted by injecting diphtheria toxin. mBD-14 does not suppress sensitization in IL-10 knockout mice, suggesting invo... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514605 Wed, 14 Dec 2011 05:00:00 +0100 5514605 http://www.medworm.com/index.php?rid=5514604&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22174456%26dopt%3DAbstract In this study, we focused on recombinant MPT83 (rMPT83) to determine its effects on mouse macrophages. We demonstrated that rMPT83 induced the production of TNF-α, IL-6, and IL-12 p40 and that cytokine induction depended on activated MAPKs, because we observed the rapid phosphorylation of ERK1/2, p38, and JNK in macrophages. Additionally, neutralizing Abs against TLR2 significantly inhibited cytokine secretion and reduced or attenuated the rMPT83-induced activation of p38 and JNK in RAW264.7 cells, a mouse macrophage cell line. Furthermore, rMPT83-induced cytokine production was significantly lower in macrophages from TLR2(-/-) mice than in macrophages from wild-type mice. We further found that prolonged exposure (>24 h) of RAW264.7 cells or macrophages from wild-type and TLR2(-/-) mic... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514604 Wed, 14 Dec 2011 05:00:00 +0100 5514604 http://www.medworm.com/index.php?rid=5494132&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22147765%26dopt%3DAbstract In this study, we show that, compared with wild-type mice, animals with a disrupted Hrh4 (H(4)RKO) develop more severe myelin oligodendrocyte glycoprotein (MOG)(35\x{2013}55)-induced experimental allergic encephalomyelitis. Mechanistically, we also show that H(4)R plays a role in determining the frequency of T regulatory (T(R)) cells in secondary lymphoid tissues, and regulates T(R) cell chemotaxis and suppressor activity. Moreover, the lack of H(4)R leads to an impairment of an anti-inflammatory response due to fewer T(R) cells in the CNS during the acute phase of the disease and an increase in the proportion of Th17 cells. PMID: 22147765 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5494132 Mon, 05 Dec 2011 05:00:00 +0100 5494132 http://www.medworm.com/index.php?rid=5494131&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22147766%26dopt%3DAbstract In this study, we demonstrate that OX40 engagement in vivo in naive mice induces initial expansion of Foxp3(+) Tregs, but the expanded Tregs have poor suppressive function and exhibit features of exhaustion. We also show that OX40 enables the activation of the Akt and Stat5 pathways in Tregs, resulting in transient proliferation of Tregs and reduced levels of Foxp3 expression. This creates a state of relative IL-2 deficiency in naive mice that further impacts Tregs. This exhausted Treg phenotype can be prevented by exogenous IL-2, as both OX40 and IL-2 agonists drive further expansion of Tregs in vivo. Importantly, Tregs expanded by both OX40 and IL-2 agonists are potent suppressor cells, and in a heart transplant model, they promote long-term allograft survival. Our data reveal a novel ro... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5494131 Mon, 05 Dec 2011 05:00:00 +0100 5494131 http://www.medworm.com/index.php?rid=5494130&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22147767%26dopt%3DAbstract Authors: Santer DM, Wiedeman AE, Teal TH, Ghosh P, Elkon KB Abstract Immune complexes (ICs) play a pivotal role in causing inflammation in systemic lupus erythematosus (SLE). Yet, it remains unclear what the dominant blood cell type(s) and inflammation-related gene programs stimulated by lupus ICs are. To address these questions, we exposed normal human PBMCs or CD14(+) isolated monocytes to SLE ICs in the presence or absence of C1q and performed microarray analysis and other tests for cell activation. By microarray analysis, we identified genes and pathways regulated by SLE ICs that are both type I IFN dependent and independent. We also found that C1q-containing ICs markedly reduced expression of the majority of IFN-response genes and also influenced the expression of multiple oth... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5494130 Mon, 05 Dec 2011 05:00:00 +0100 5494130 http://www.medworm.com/index.php?rid=5494129&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22147768%26dopt%3DAbstract Authors: Benson A, Murray S, Divakar P, Burnaevskiy N, Pifer R, Forman J, Yarovinsky F Abstract Regulatory Foxp3(+) T cells are a critical cell population that suppresses T cell activation in response to microbial and viral pathogens. We identify a cell-intrinsic mechanism by which effector CD4(+) T cells overcome the suppressive effects of regulatory T (Treg) cells in the context of three distinct infections: Toxoplasma gondii, Listeria monocytogenes, and vaccinia virus. The acute responses to the parasitic, bacterial, and viral pathogens resulted in a transient reduction in frequency and absolute number of Treg cells. The infection-induced partial loss of Treg cells was essential for the initiation of potent Th1 responses and host protection against the pathogens. The observed di... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5494129 Mon, 05 Dec 2011 05:00:00 +0100 5494129 http://www.medworm.com/index.php?rid=5475831&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140254%26dopt%3DAbstract Authors: Huijbers IJ, Soudja SM, Uyttenhove C, Buferne M, Inderberg-Suso EM, Colau D, Pilotte L, Powis de Tenbossche CG, Chomez P, Brasseur F, Schmitt-Verhulst AM, Van den Eynde BJ Abstract Central tolerance toward tissue-restricted Ags is considered to rely on ectopic expression in the thymus, which was also observed for tumor Ags encoded by cancer-germline genes. It is unknown whether endogenous expression shapes the T cell repertoire against the latter Ags and explains their weak immunogenicity. We addressed this question using mouse cancer-germline gene P1A, which encodes antigenic peptide P1A(35-43) presented by H-2L(d). We made P1A-knockout (P1A-KO) mice and asked whether their anti-P1A(35-43) immune responses were stronger than those of wild-type mice and whether P1A-KO mice... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475831 Fri, 02 Dec 2011 05:00:00 +0100 5475831 http://www.medworm.com/index.php?rid=5475830&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140255%26dopt%3DAbstract In conclusion, we demonstrate that MC presence protects mice from VV skin infection, MC degranulation is required for protecting mice from VV, neutralizing Ab to the L1 fusion entry protein of VV inhibits degranulation apparently by preventing S1PR2 activation by viral membrane lipids, and antimicrobial peptide release from MC granules is necessary to inactivate VV infectivity. PMID: 22140255 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475830 Fri, 02 Dec 2011 05:00:00 +0100 5475830 http://www.medworm.com/index.php?rid=5475829&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140256%26dopt%3DAbstract Authors: Wenzel M, Wunderlich M, Besch R, Poeck H, Willms S, Schwantes A, Kremer M, Sutter G, Endres S, Schmidt A, Rothenfusser S Abstract A key host response to limit microbial spread is the induction of cell death when foreign nucleic acids are sensed within infected cells. In mouse macrophages, transfected DNA or infection with modified vaccinia virus Ankara (MVA) can trigger cell death via the absent in melanoma 2 (AIM2) inflammasome. In this article, we show that nonmyeloid human cell types lacking a functional AIM2 inflammasome still die in response to cytosolic delivery of different DNAs or infection with MVA. This cell death induced by foreign DNA is independent of caspase-8 and carries features of mitochondrial apoptosis: dependence on BAX, APAF-1, and caspase-9. Although ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475829 Fri, 02 Dec 2011 05:00:00 +0100 5475829 http://www.medworm.com/index.php?rid=5475828&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140257%26dopt%3DAbstract In this study, we provide new evidence that cholesterol biosynthesis is important to myeloid cell growth and is supported by the sterol reductase domain of Lbr. Cholesterol biosynthesis inhibitors caused growth inhibition of EML cells that increased in EML-derived promyelocytes, whereas cells lacking Lbr exhibited complete growth arrest at both stages. Lipid production increased during wild-type neutrophil maturation, but ic/ic cells exhibited deficient levels of lipid and cholesterol production. Ectopic expression of a full-length Lbr in EML-ic/ic cells rescued both nuclear lobulation and growth arrest in cholesterol starvation conditions. Lipid production also was rescued, and a deficient respiratory burst was corrected. Expression of just the C-terminal sterol reductase domain of Lbr in... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475828 Fri, 02 Dec 2011 05:00:00 +0100 5475828 http://www.medworm.com/index.php?rid=5475827&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140258%26dopt%3DAbstract In this study, we investigated how three TCRs, which differ in their T cell immunodominance hierarchies and gene usage, interact with the same EBV determinant (FLRGRAYGL), bound to the same Ag-presenting molecule, HLA-B8. We found that the three TCRs exhibit differing fine specificities for the viral Ag. Further, via structural and biophysical approaches, we demonstrated that the viral Ag provides the greatest energetic contribution to the TCR-peptide-HLA interaction, while focusing on a few adjacent HLA-based interactions to further tune fine-specificity requirements. Thus, the TCR engages the peptide-HLA with the viral Ag as the main glue, such that neighboring TCR-MHC interactions are recruited as a supportive adhesive. Collectively, we provide a portrait of how the host's adaptive immu... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475827 Fri, 02 Dec 2011 05:00:00 +0100 5475827 http://www.medworm.com/index.php?rid=5475826&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140259%26dopt%3DAbstract In this study, we found that activation of human complement by different GAS strains (n = 38) correlated negatively with binding of CFH via its domains 5-7. The importance of acquisition of host CFH for survival of GAS in vitro was studied next by blocking the binding with recombinant CFH5-7 lacking the regulatory domains 1-4. Using this fragment in full human blood resulted in death or radically reduced multiplication of all of the studied CFH-binding GAS strains. To study the importance of CFH binding in vivo (i.e., for pathogenesis of streptococcal infections), we used our recent finding that GAS binding to CFH is diminished in vitro by polymorphism 402H, which is also associated with age-related macular degeneration. We showed that allele 402H is suggested to be associated with protect... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475826 Fri, 02 Dec 2011 05:00:00 +0100 5475826 http://www.medworm.com/index.php?rid=5475825&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140260%26dopt%3DAbstract In this study, using PCR to analyze the Ab response to phenyl-oxazolone in the mouse, we show that the Ab repertoire of CD21(hi)/CD23(-) marginal zone B cells shows persistent increase in levels of particular IgM after immunization with foreign Ag. Further, we show that these IgMs have different but related VH/CDR3 sequences from those seen in the class-switched response to oxazolone that we have also analyzed. We also detect an effect of Ag on the follicular B cell repertoire that is less persisting. These results provide evidence consistent with the signal-strength model of mature B cell development being extended to include stimulation by foreign Ag, and also further the known zone of influence of foreign Ag on the B cell compartment. PMID: 22140260 [PubMed - as supplied by publishe... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475825 Fri, 02 Dec 2011 05:00:00 +0100 5475825 http://www.medworm.com/index.php?rid=5475824&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140261%26dopt%3DAbstract In this study, we investigated the regulatory role of Gr1(+)CD11b(+) cells in protecting against type 1 diabetes in NOD mice. In this study, we showed that temporary B cell depletion induced the expansion of Gr1(+)CD11b(+) cells. Gr1(+)CD11b(+) cells not only directly suppress diabetogenic T cell function but also can induce regulatory T cell differentiation in a TGF-β-dependent manner. Furthermore, we found that Gr1(+)CD11b(+) cells could suppress diabetogenic CD4 and CD8 T cell function in an IL-10-, NO-, and cell contact-dependent manner. Interestingly, single anti-Gr1 mAb treatment can also induce a transient expansion of Gr1(+)CD11b(+) cells that delayed diabetes development in NOD mice. Our data suggest that Gr1(+)CD11b(+) cells contribute to the establishment of immune tolerance to... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475824 Fri, 02 Dec 2011 05:00:00 +0100 5475824 http://www.medworm.com/index.php?rid=5475823&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140262%26dopt%3DAbstract In this study, we describe a novel biological mechanism essential for survival and homeostasis of normal peripheral mature B cells and chronic lymphocytic leukemia cells, regulated by the heparin-binding cytokine, midkine (MK), and its proteoglycan receptor, the receptor-type tyrosine phosphatase ζ (RPTPζ). We demonstrate that MK initiates a signaling cascade leading to B cell survival by binding to RPTPζ. In mice lacking PTPRZ, the proportion and number of the mature B cell population are reduced. Our results emphasize a unique and critical function for MK signaling in the previously described MIF/CD74-induced survival pathway. Stimulation of CD74 with MIF leads to c-Met activation, resulting in elevation of MK expression in both normal mouse splenic B and chronic lymphocytic leukemia ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475823 Fri, 02 Dec 2011 05:00:00 +0100 5475823 http://www.medworm.com/index.php?rid=5475822&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140263%26dopt%3DAbstract In this study, we investigated the regulation of IL-10 production by macrophages infected with Leishmania donovani. Infection of either murine or human macrophages brought about selective phosphorylation of Akt-2 in a PI3K-dependent manner. These events were linked to phosphorylation and inactivation of glycogen synthase kinase-3β (GSK-3β) at serine 9, as the latter was abrogated by inhibition of either PI3K or Akt. One of the transcription factors that is negatively regulated by GSK-3β is CREB, which itself positively regulates IL-10 expression. Infection of macrophages with leishmania induced phosphorylation of CREB at serine 133, and this was associated with enhanced CREB DNA binding activity and induction of IL-10. Similar to phosphorylation of GSK-3β, both phosphorylation of CREB ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475822 Fri, 02 Dec 2011 05:00:00 +0100 5475822 http://www.medworm.com/index.php?rid=5457108&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22124119%26dopt%3DAbstract Authors: Nishiura H, Kido M, Aoki N, Iwamoto S, Maruoka R, Ikeda A, Chiba T, Ziegler SF, Watanabe N Abstract Thymic stromal lymphopoietin (TSLP), mainly produced by epithelial cells, activates a variety of cell types, including dendritic cells, mast cells, T cells, and B cells. It is involved in the pathogenesis of allergic inflammation in the lung, skin, and gastrointestinal tract. In addition, TSLP promotes Th2-type intestinal immunity against helminth infection and regulates Th1-type inflammation in a mouse model of colitis, suggesting that it plays crucial roles in intestinal immune homeostasis. Although autoimmune gastritis (AIG), mediated by inflammatory Th1 responses, develops in the gastric mucosa, it is not clear whether TSLP is involved in regulating these responses in AI... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5457108 Mon, 28 Nov 2011 05:00:00 +0100 5457108 http://www.medworm.com/index.php?rid=5457107&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22124120%26dopt%3DAbstract Authors: Kreuzaler M, Rauch M, Salzer U, Birmelin J, Rizzi M, Grimbacher B, Plebani A, Lougaris V, Quinti I, Thon V, Litzman J, Schlesier M, Warnatz K, Thiel J, Rolink AG, Eibel H Abstract The TNF family member protein BAFF/BLyS is essential for B cell survival and plays an important role in regulating class switch recombination as well as in the selection of autoreactive B cells. In humans, increased concentrations of soluble BAFF are found in different pathological conditions, which may be as diverse as autoimmune diseases, B cell malignancies, and primary Ab deficiencies (PAD). Because the mechanisms that regulate BAFF levels are not well understood, we newly developed a set of mAbs against human BAFF to study the parameters that determine the concentrations of soluble BAFF in c... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5457107 Mon, 28 Nov 2011 05:00:00 +0100 5457107 http://www.medworm.com/index.php?rid=5457104&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22124121%26dopt%3DAbstract Authors: Liu SM, Sutherland AP, Zhang Z, Rainbow DB, Quintana FJ, Paterson AM, Sharpe AH, Oukka M, Wicker LS, Kuchroo VK Abstract CTLA-4 is a potent inhibitor of T cell activation, primarily upon binding to its costimulatory ligands (B7.1 and B7.2) expressed on APCs. However, variants of CTLA-4 can also function independently of B7 molecules. 1/4CTLA-4 is a highly conserved isoform encoded by exons 1 and 4 of the Ctla4 gene that lacks the ligand-binding and the transmembrane domains, and as yet, its function is not known. To investigate the function of 1/4CTLA-4, we generated transgenic (Tg) mice overexpressing this variant. Cytokine production by 1/4CTLA-4 Tg T cells was elevated compared with wild type T cells. The frequency of CD44(high) memory T cells in 1/4CTLA-4 Tg mice was i... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5457104 Mon, 28 Nov 2011 05:00:00 +0100 5457104 http://www.medworm.com/index.php?rid=5457086&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22124122%26dopt%3DAbstract Authors: Kim J, Kim DW, Chang W, Choe J, Kim J, Park CS, Song K, Lee I Abstract Follicular dendritic cells (FDCs) protect germinal center (GC) B cells from rapid apoptosis to allow their survival and maturation. In this article, we show that FDCs normally produce and secrete Wnt5a to protect GC B cells. Wnt5a production is upregulated by polyI:C. Purified Wnt5a protects GC B cells from apoptosis in a dose-dependent manner. GC B cells are protected by FDC coculture or conditioned medium, and the protection is inhibited significantly by anti-Wnt5a Ab, suggesting a major role of Wnt5a in the FDC-mediated GC B cell protection. A calcium chelator BAPTA-AM blocks the Wnt5a-mediated GC B cell protection, implying a role of Wnt/Ca(2+) signaling in the GC B cell survival. Wnt5a and calcium ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5457086 Mon, 28 Nov 2011 05:00:00 +0100 5457086 http://www.medworm.com/index.php?rid=5457077&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22124123%26dopt%3DAbstract Authors: Barthel D, Singh B, Riesbeck K, Zipfel PF Abstract Pathogenic microbes acquire the human plasma protein plasminogen to their surface. In this article, we characterize binding of this important coagulation regulator to the respiratory pathogen nontypeable Haemophilus influenzae and identify the Haemophilus surface protein E (PE) as a new plasminogen-binding protein. Plasminogen binds dose dependently to intact bacteria and to purified PE. The plasminogen-PE interaction is mediated by lysine residues and is also affected by ionic strength. The H. influenzae PE knockout strain (nontypeable H. influenzae 3655Δpe) bound plasminogen with ∼65% lower intensity as compared with the wild-type, PE-expressing strain. In addition, PE expressed ectopically on the surface of Escherich... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5457077 Mon, 28 Nov 2011 05:00:00 +0100 5457077 http://www.medworm.com/index.php?rid=5457076&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22124124%26dopt%3DAbstract Authors: Martinez RJ, Zhang N, Thomas SR, Nandiwada SL, Jenkins MK, Binstadt BA, Mueller DL Abstract Rheumatoid arthritis develops in association with a defect in peripheral CD4(+) T cell homeostasis. T cell lymphopenia has also been shown to be a barrier to CD4(+) T cell clonal anergy induction. We therefore explored the relationship between clonal anergy induction and the avoidance of autoimmune arthritis by tracking the fate of glucose-6-phosphate isomerase (GPI)-reactive CD4(+) T cells in the setting of selective T cell lymphopenia. CD4(+) T cell recognition of self-GPI peptide/MHC class II complexes in normal murine hosts did not lead to arthritis and instead caused those T cells to develop a Folate receptor 4(hi)CD73(hi) anergic phenotype. In contrast, hosts selectively deple... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5457076 Mon, 28 Nov 2011 05:00:00 +0100 5457076 http://www.medworm.com/index.php?rid=5457075&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22124125%26dopt%3DAbstract In this study, we investigated the effects of hypoxic exposure and/or the administration of dexamethasone (Dex), a synthetic GC on GILZ expression both in vitro and in vivo, and further explored the relationship between GILZ and proinflammatory cytokines IL-1β, IL-6, and TNF-α under normoxic and hypoxic conditions. We found that hypoxia not only remarkably upregulated the expression of GILZ, but also significantly enhanced Dex-induced expression of GILZ in macrophages and the spleen of rats. ERK activity is found involved in the upregulation of GILZ induced by hypoxia. Inhibiting the expression of GILZ in RAW264.7 cells using specific GILZ small interfering RNA led to a significant increase in mRNA production and protein secretion of IL-1β and IL-6 in hypoxia and abrogated the inhibitor... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5457075 Mon, 28 Nov 2011 05:00:00 +0100 5457075 http://www.medworm.com/index.php?rid=5457074&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22124126%26dopt%3DAbstract Authors: Nigro EA, Soprana E, Brini AT, Ambrosi A, Yenagi VA, Dombrowicz D, Siccardi AG, Vangelista L Abstract The IgE-mediated immune system activation can be redirected to combat tumors. Mouse and human IgE have been shown to provide a potent adjuvant effect in antitumor vaccination, with a crucial role played by FcεRI. This effect results from T cell-mediated adaptive immune response. Modified vaccinia virus Ankara (MVA) has been used to infect IgE-loaded tumor cells. These results led to a shift toward a highly safe protocol employing membrane IgE (mIgE), thus eliminating any possible anaphylactogenicity caused by circulating IgE. Evidence that human mIgE and a truncated version lacking IgE Fabs (tmIgE) bind and activate FcεRI has been fundamental and forms the core of this r... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5457074 Mon, 28 Nov 2011 05:00:00 +0100 5457074 http://www.medworm.com/index.php?rid=5441175&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22105994%26dopt%3DAbstract Authors: Xu LG, Jin L, Zhang BC, Akerlund LJ, Shu HB, Cambier JC Abstract B cells play a critical role in the initialization and development of the systemic lupus erythematosus that is dependent on the expression of the endosomal ssRNA receptor TLR7. Previous studies have established that B cell expression of TLR7 is controlled by the type I IFN secreted by plasmacytoid dendritic cells. In this article, we report that VISA, also known as MAVS, IPS-1, and CardIf, essential for RIG-I/MDA5-mediated signaling following sensing of cytosolic RNA, regulate B cell expression of TLR7 and CD23. We found that B cells from a VISA(-/-) mouse express reduced TLR7 but normal basal levels of type I IFN. We also show that although IFN-β and TLR7 agonists synergize to promote TLR7 expression in VIS... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5441175 Mon, 21 Nov 2011 05:00:00 +0100 5441175 http://www.medworm.com/index.php?rid=5441174&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22105995%26dopt%3DAbstract Authors: Philippe L, Alsaleh G, Suffert G, Meyer A, Georgel P, Sibilia J, Wachsmann D, Pfeffer S Abstract Resident cells, such as fibroblast-like synoviocytes (FLS), play a crucial role in rheumatoid arthritis (RA). They are implicated in the inflammatory response and play a key role in osteoarticular destruction. Moreover, RA FLS spread RA to unaffected joints. Pathogen-associated molecular patterns and damage-associated molecular patterns have been found to activate RA FLS by interacting with pattern recognition receptors, such as TLR. RA FLS express a large number of TLR, and TLR2 was demonstrated to be involved in RA inflammation. Because microRNA have emerged as important controllers of TLR expression and signaling, the aim of this study was to evaluate their potential involve... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5441174 Mon, 21 Nov 2011 05:00:00 +0100 5441174 http://www.medworm.com/index.php?rid=5441173&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22105996%26dopt%3DAbstract Authors: Habib T, Funk A, Rieck M, Brahmandam A, Dai X, Panigrahi AK, Luning Prak ET, Meyer-Bahlburg A, Sanda S, Greenbaum C, Rawlings DJ, Buckner JH Abstract The PTPN22 genetic variant 1858T, encoding Lyp620W, is associated with multiple autoimmune disorders for which the production of autoantibodies is a common feature, suggesting a loss of B cell tolerance. Lyp620W results in blunted BCR signaling in memory B cells. Because BCR signal strength is tightly coupled to central and peripheral tolerance, we examined whether Lyp620W impacts peripheral B cell homeostasis in healthy individuals heterozygous for the PTPN221858T variant. We found that these subjects display alterations in the composition of the B cell pool that include specific expansion of the transitional and anergic IgD... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5441173 Mon, 21 Nov 2011 05:00:00 +0100 5441173 http://www.medworm.com/index.php?rid=5441172&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22105997%26dopt%3DAbstract Authors: Kerzerho J, Wunsch D, Szely N, Meyer HA, Lurz L, Röse L, Wahn U, Akbari O, Stock P Abstract Respiratory exposure to allergen induces T cell tolerance and protection against the development of airway hyperactivity in animal models of asthma. Whereas systemic administration of dexamethasone during the delivery of respiratory Ag has been suggested to prevent the development of mucosal tolerance, the effects of local administration of corticosteroids, first-line treatment for patients with bronchial asthma, on mucosal tolerance remain unknown. To analyze the effects of systemic versus local administration of different types of corticosteroids on the development of mucosal tolerance, mice were exposed to respiratory allergen to induce mucosal tolerance with or without systemic... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5441172 Mon, 21 Nov 2011 05:00:00 +0100 5441172 http://www.medworm.com/index.php?rid=5441171&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22105998%26dopt%3DAbstract We describe a mouse pedigree, Lym3, with normal bone marrow and thymic development but profound and progressive lymphopenia particularly within the T cell compartment. This defect arises from a point mutation within the Lbr gene with only trace mutant protein detectable in homozygotes, albeit sufficient for normal development. Reduced T cell homeostatic proliferative potential and life span in vivo were found to contribute to lymphopenia. To investigate the role of LBR in gene silencing in hematopoietic cells, we examined gene expression in wild-type and mutant lymph node CD8 T cells and bone marrow neutrophils. Although LBR deficiency had a very mild impact on gene expression overall, for common genes differentially expressed in both LBR-deficient CD8 T cells and neutrophils, gene upregul... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5441171 Mon, 21 Nov 2011 05:00:00 +0100 5441171 http://www.medworm.com/index.php?rid=5441170&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22105999%26dopt%3DAbstract Authors: Muñoz-Fontela C, Pazos M, Delgado I, Murk W, Mungamuri SK, Lee SW, García-Sastre A, Moran TM, Aaronson SA Abstract Several direct target genes of the p53 tumor suppressor have been identified within pathways involved in viral sensing, cytokine production, and inflammation, suggesting a potential role of p53 in antiviral immunity. The increasing need to identify immune factors to devise host-targeted therapies against pandemic influenza A virus (IAV) led us to investigate the role of endogenous wild-type p53 on the immune response to IAV. We observed that the absence of p53 resulted in delayed cytokine and antiviral gene responses in lung and bone marrow, decreased dendritic cell activation, and reduced IAV-specific CD8(+) T cell immunity. Consequently, p53(-/-) mice show... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5441170 Mon, 21 Nov 2011 05:00:00 +0100 5441170 http://www.medworm.com/index.php?rid=5441169&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22106000%26dopt%3DAbstract In this study, we identify the molecular pathways that contribute to the onset of colitis in Gimap5(sph/sph) mice. We show that CD4(+) T cells become Th1/Th17 polarized and are critically important for the development of colitis. Concomitantly, regulatory T cells become reduced in frequency in the peripheral tissues, and their immunosuppressive capacity becomes impaired. Most importantly, these progressive changes in CD4(+) T cells are associated with the loss of Forkheadbox group O (Foxo)1, Foxo3, and Foxo4 expression. Our data establish a novel link between Gimap5 and Foxo expression and provide evidence for a regulatory mechanism that controls Foxo protein expression and may help to maintain immunological tolerance. PMID: 22106000 [PubMed - as supplied by publisher] (Source: Journal... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5441169 Mon, 21 Nov 2011 05:00:00 +0100 5441169 http://www.medworm.com/index.php?rid=5381821&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22049227%26dopt%3DAbstract Authors: Kolset SO, Pejler G Abstract Among the different proteoglycans expressed by mammals, serglycin is in most immune cells the dominating species. A unique property of serglycin is its ability to adopt highly divergent structures, because of glycosylation with variable types of glycosaminoglycans when expressed by different cell types. Recent studies of serglycin-deficient animals have revealed crucial functions for serglycin in a diverse array of immunological processes. However, its exact function varies to a large extent depending on the cellular context of serglycin expression. Based on these findings, serglycin is emerging as a structural and functional chameleon, with radically different properties depending on its exact cellular and immunological context. PMID: 2204... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381821 Mon, 07 Nov 2011 08:26:13 +0100 5381821 http://www.medworm.com/index.php?rid=5381833&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048764%26dopt%3DAbstract Authors: Cohen CJ, Crome SQ, Macdonald KG, Dai EL, Mager DL, Levings MK Abstract The linear model of Th cell lineage commitment is being revised due to reports that mature Th cells can trans-differentiate into alternate lineages. This ability of Th cells to reprogram is thought to be regulated by epigenetic mechanisms that control expression of transcription factors characteristic of opposing lineages. It is unclear, however, to what extent this new model of Th cell plasticity holds true in human Th cell subsets that develop under physiological conditions in vivo. We isolated in vivo-differentiated human Th1 and Th17 cells, as well as intermediate Th1/17 cells, and identified distinct epigenetic signatures at cytokine (IFNG and IL17A) and transcription factor (TBX21, RORC, and RORA... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381833 Wed, 02 Nov 2011 04:00:00 +0100 5381833 http://www.medworm.com/index.php?rid=5381832&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048765%26dopt%3DAbstract Authors: McKinnon LR, Nyanga B, Chege D, Izulla P, Kimani M, Huibner S, Gelmon L, Block KE, Cicala C, Anzala AO, Arthos J, Kimani J, Kaul R Abstract The HIV pandemic disproportionately affects women, with most infections acquired through receptive vaginal sex. Although the target cells by which HIV establishes infection in the female genital tract remain poorly defined, it is known that immune activation results in CD4(+) T cells with enhanced susceptibility, as does expression of the mucosal integrin α4β7 and the HIV coreceptor CCR5. Blood and cervical cytobrush specimens were collected from female sex workers (FSWs) in Nairobi, Kenya. Genital infection diagnostics were performed, T cell populations were defined by multiparameter flow cytometry based on their expression of surfa... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381832 Wed, 02 Nov 2011 04:00:00 +0100 5381832 http://www.medworm.com/index.php?rid=5381831&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048766%26dopt%3DAbstract Authors: Jacobsen EA, Zellner KR, Colbert D, Lee NA, Lee JJ Abstract Reports have recently suggested that eosinophils have the potential to modulate allergen-dependent pulmonary immune responses. The studies presented expand these reports demonstrating in the mouse that eosinophils are required for the allergen-dependent Th2 pulmonary immune responses mediated by dendritic cells (DCs) and T lymphocytes. Specifically, the recruitment of peripheral eosinophils to the pulmonary lymphatic compartment(s) was required for the accumulation of myeloid DCs in draining lymph nodes and, in turn, Ag-specific T effector cell production. These effects on DCs and Ag-specific T cells did not require MHC class II expression on eosinophils, suggesting that these granulocytes have an accessory role a... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381831 Wed, 02 Nov 2011 04:00:00 +0100 5381831 http://www.medworm.com/index.php?rid=5381830&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048767%26dopt%3DAbstract In this study, we report that bone marrow cells from wild-type C57BL/6 mice responded with IL-5 and IL-13 production when cultured with IL-33. IL-33 cultures of bone marrow cells from Rag1 KO and Kit(W-sh/W-sh) mice also responded similarly; hence, eliminating the possible contributions of T, B, and mast cells. Rather, intracellular staining revealed that the IL-5- and IL-13-positive cells display a marker profile consistent with the Lineage(-)Sca-1(+)c-Kit(-)CD25(+) (LSK(-)CD25(+)) cells, a bone marrow cell population of previously unknown function. Freshly isolated LSK(-)CD25(+) cells uniformly express ST2, the IL-33 receptor. In addition, culture of sorted LSK(-)CD25(+) cells showed that they indeed produce IL-5 and IL-13 when cultured with IL-33 plus IL-2 and IL-33 plus IL-7. Furthermo... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381830 Wed, 02 Nov 2011 04:00:00 +0100 5381830 http://www.medworm.com/index.php?rid=5381829&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048768%26dopt%3DAbstract Authors: Alfaro C, Perez-Gracia JL, Suarez N, Rodriguez J, Fernandez de Sanmamed M, Sangro B, Martin-Algarra S, Calvo A, Redrado M, Agliano A, Gonzalez A, Rodriguez I, Bolaños E, Hervás-Stubbs S, Perez-Calvo J, Benito A, Peñuelas I, Vigil C, Richter J, Martinez-Forero I, Melero I Abstract Twenty-four patients with metastatic cancer received two cycles of four daily immunizations with monocyte-derived dendritic cells (DC). DC were incubated with preheated autologous tumor lysate and subsequently with IFN-α, TNF-α, and polyinosinic:polycytidylic acid to attain type 1 maturation. One DC dose was delivered intranodally, under ultrasound control, and the rest intradermally in the opposite thigh. Cyclophosphamide (day -7), GM-CSF (days 1-4), and pegIFN alpha-2a (days 1 and 8) comple... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381829 Wed, 02 Nov 2011 04:00:00 +0100 5381829 http://www.medworm.com/index.php?rid=5381828&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048769%26dopt%3DAbstract This study demonstrates that CB2 positively regulates T-independent immune responses by controlling the localization and positioning of MZ lineage cells to the MZ. PMID: 22048769 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381828 Wed, 02 Nov 2011 04:00:00 +0100 5381828 http://www.medworm.com/index.php?rid=5381827&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048770%26dopt%3DAbstract In this study, we report that splenic murine B cells express very little HS and that upon infection with either gammaherpesvirus (murine gammaherpesvirus 68) or betaherpesvirus (murine cytomegalovirus), HS is rapidly upregulated at the surface of B cells. HS upregulation was not observed in mice deficient for the type I IFN (IFN-I) receptor. Additionally, treatment of wild-type mice with the IFN-I inducer polyinosine polycytidylic acid triggered HS expression at the B cell surface. Similarly, incubation of purified splenic B cells with IFN-I, TLR ligands, or BCR stimulators ex vivo resulted in a drastic increase in HS surface expression. We found that IFN-I induced an increase in the surface expression of HS-modified syndecan 4 as well as that of an unidentified heparan sulfate proteoglyca... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381827 Wed, 02 Nov 2011 04:00:00 +0100 5381827 http://www.medworm.com/index.php?rid=5381826&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048771%26dopt%3DAbstract In this study, we show that upon costimulation of the TCR with CD28 or signaling lymphocyte activation molecule (SLAM), DGKα, but not DGKζ, exits from the nucleus and undergoes rapid negative regulation of its enzymatic activity. Inhibition of DGKα is dependent on the expression of SAP, an adaptor protein mutated in X-linked lymphoproliferative disease, which is essential for SLAM-mediated signaling and contributes to TCR/CD28-induced signaling and T cell activation. Accordingly, overexpression of SAP is sufficient to inhibit DGKα, whereas SAP mutants unable to bind either phospho-tyrosine residues or SH3 domain are ineffective. Moreover, phospholipase C activity and calcium, but not Src-family tyrosine kinases, are also required for negative regulation of DGKα. Finally, inhibition of... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381826 Wed, 02 Nov 2011 04:00:00 +0100 5381826 http://www.medworm.com/index.php?rid=5381825&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048772%26dopt%3DAbstract In this study, we show that TLR3 signaling was not enhanced, but was dramatically inhibited, by LL37 or mouse cathelicidin-related antimicrobial peptide in macrophages, microglial cells, and dendritic cells. Inhibition correlated with formation of a strong complex between antimicrobial peptides and poly(I:C), which partially inhibited poly(I:C) binding to TLR3. Therefore, after injury or during existing acute or chronic inflammation, when LL37 levels are elevated, the therapeutic activity of poly(I:C) will be compromised. Our findings highlight the importance of using caution when therapeutically delivering nucleic acids as immunomodulators. PMID: 22048772 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381825 Wed, 02 Nov 2011 04:00:00 +0100 5381825 http://www.medworm.com/index.php?rid=5381824&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048773%26dopt%3DAbstract Authors: Park SY, Gupta D, Hurwich R, Kim CH, Dziarski R Abstract Skin protects the body from the environment and is an important component of the innate and adaptive immune systems. Psoriasis is a frequent inflammatory skin disease of unknown cause determined by multigenic predisposition, environmental factors, and aberrant immune response. Peptidoglycan recognition proteins (Pglyrps) are expressed in the skin, and we report in this article that they modulate sensitivity in an experimentally induced mouse model of psoriasis. We demonstrate that Pglyrp2(-/-) mice (but not Pglyrp3(-/-) and Pglyrp4(-/-) mice) are more sensitive to the development of 12-O-tetradecanoylphorbol 13-acetate-induced psoriasis-like inflammation, whereas Pglyrp1(-/-) mice are less sensitive. The mechanism un... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381824 Wed, 02 Nov 2011 04:00:00 +0100 5381824 http://www.medworm.com/index.php?rid=5381823&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048774%26dopt%3DAbstract Authors: Zaynagetdinov R, Sherrill TP, Polosukhin VV, Han W, Ausborn JA, McLoed AG, McMahon FB, Gleaves LA, Degryse AL, Stathopoulos GT, Yull FE, Blackwell TS Abstract Macrophages have established roles in tumor growth and metastasis, but information about their role in lung tumor promotion is limited. To assess the role of macrophages in lung tumorigenesis, we developed a method of minimally invasive, long-term macrophage depletion by repetitive intratracheal instillation of liposomal clodronate. Compared with controls treated with repetitive doses of PBS-containing liposomes, long-term macrophage depletion resulted in a marked reduction in tumor number and size at 4 mo after a single i.p. injection of the carcinogen urethane. After urethane treatment, lung macrophages developed i... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381823 Wed, 02 Nov 2011 04:00:00 +0100 5381823 http://www.medworm.com/index.php?rid=5381822&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048775%26dopt%3DAbstract Authors: Hebel K, Rudolph M, Kosak B, Chang HD, Butzmann J, Brunner-Weinzierl MC Abstract Cytokines are critical messengers that control the differentiation of Th cells. To evaluate their impact on the fate of human naive CD4(+) T cells from cord and adult blood, early T cell differentiation was monitored after T cell activation in the presence of pro- and anti-inflammatory cytokines. Interestingly, the analysis of Th cell lineage-specific molecules revealed that IL-1β on its own mediates differentiation of Th cells that secrete a wide range of proinflammatory cytokines and stably express CD69, STAT1, IFN-γ, and IL-17. Notably, our data suggest that IL-1β induces Th17 cells independent of RORC upregulation. In contrast, TGF-β that triggers RORC prevents Th17 cell development. T... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5381822 Wed, 02 Nov 2011 04:00:00 +0100 5381822 http://www.medworm.com/index.php?rid=5361877&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22031758%26dopt%3DAbstract Authors: Chen M, Felix K, Wang J Abstract Dendritic cells (DCs) harbor an active mitochondrion-dependent cell death pathway regulated by Bcl-2 family members and undergo rapid turnover in vivo. However, the functions for mitochondrion-dependent cell death of DCs in immune regulation remain to be elucidated. In this article, we show that DC-specific knockout of proapoptotic Bcl-2 family members, Bax and Bak, induced spontaneous T cell activation and autoimmunity in mice. In addition to a defect in spontaneous cell death, Bax(-/-)Bak(-/-) DCs were resistant to killing by CD4(+)Foxp3(+) T regulatory cells (Tregs) compared with wild-type DCs. Tregs inhibited the activation of T effector cells by wild-type, but not Bax(-/-)Bak(-/-), DCs. Bax(-/-)Bak(-/-) DCs showed increased propensity ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5361877 Wed, 26 Oct 2011 04:00:00 +0100 5361877 http://www.medworm.com/index.php?rid=5361876&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22031759%26dopt%3DAbstract In conclusion, the results highlight a novel role for RSK1/2 and HSP27 phosphoproteins and of the cooperative role of the TFs NF-κB, NF-IL6, AP-1, CHOP, and CREB in P. aeruginosa-dependent induction of transcription of the IL-8 gene in human bronchial epithelial cells. PMID: 22031759 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5361876 Wed, 26 Oct 2011 04:00:00 +0100 5361876 http://www.medworm.com/index.php?rid=5361875&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22031760%26dopt%3DAbstract Authors: Montecino-Rodriguez E, Dorshkind K Abstract The stages of development leading up to the formation of mature B-1 cells have not been identified. As a result, there is no basis for understanding why various genetic defects, and those in the classical or alternative NF-κB pathways in particular, differentially affect the B-1 and B-2 B cell lineages. In this article, we demonstrate that B-1 B cells are generated from transitional cell intermediates that emerge in a distinct neonatal wave of development that is sustained for ∼2 wk after birth and then declines as B-2 transitional cells predominate. We further show that, in contrast to the dependence of B-2 transitional cells on the alternative pathway, the survival of neonatal B-1 transitional cells and their maturation into... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5361875 Wed, 26 Oct 2011 04:00:00 +0100 5361875 http://www.medworm.com/index.php?rid=5361874&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22031761%26dopt%3DAbstract Authors: Huang Y, Biswas C, Klos Dehring DA, Sriram U, Williamson EK, Li S, Clarke F, Gallucci S, Argon Y, Burkhardt JK Abstract The hematopoietic actin regulatory protein hematopoietic lineage cell-specific protein 1 (HS1) is required for cell spreading and signaling in lymphocytes, but the scope of HS1 function in Ag presentation has not been addressed. We show that dendritic cells (DCs) from HS1(-/-) mice differentiate normally and display normal LPS-induced upregulation of surface markers and cytokines. Consistent with their normal expression of MHC and costimulatory molecules, HS1(-/-) DCs present OVA peptide efficiently to CD4(+) T cells. However, presentation of OVA protein is defective. Similarly, MHC class I-dependent presentation of VSV8 peptide to CD8(+) T cells occurs n... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5361874 Wed, 26 Oct 2011 04:00:00 +0100 5361874 http://www.medworm.com/index.php?rid=5361873&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22031762%26dopt%3DAbstract Authors: Wolf AJ, Arruda A, Reyes CN, Kaplan AT, Shimada T, Shimada K, Arditi M, Liu G, Underhill DM Abstract Signaling by innate immune receptors initiates and orchestrates the overall immune responses to infection. Macrophage receptors recognizing pathogens can be broadly grouped into surface receptors and receptors restricted to intracellular compartments, such as phagosomes and the cytoplasm. There is an expectation that ingestion and degradation of microorganisms by phagocytes contributes to activation of intracellular innate receptors, although direct demonstrations of this are rare, and many model ligands are studied in soluble form, outside of their microbial context. By comparing a wild-type strain of Staphylococcus aureus and a lysozyme-sensitive mutant, we have been able... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5361873 Wed, 26 Oct 2011 04:00:00 +0100 5361873 http://www.medworm.com/index.php?rid=5361872&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22031763%26dopt%3DAbstract Authors: Ichinose K, Rauen T, Juang YT, Kis-Toth K, Mizui M, Koga T, Tsokos GC Abstract Renal involvement in systemic lupus erythematosus remains a major cause of morbidity and mortality. Although immune parameters that instigate renal damage have been characterized, their link to local processes, which execute tissue damage, is poorly understood. Using genetic-deletion and pharmacological-inhibition approaches, we demonstrated that calcium/calmodulin-dependent protein kinase type IV, which contributes to altered cytokine production in systemic lupus erythematosus patients, controls spontaneous and platelet-derived growth factor-stimulated mesangial cell proliferation and promotes IL-6 production through AP-1. Our studies identified calcium/calmodulin-dependent protein kinase type ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5361872 Wed, 26 Oct 2011 04:00:00 +0100 5361872 http://www.medworm.com/index.php?rid=5361871&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22031764%26dopt%3DAbstract Authors: Chyou S, Benahmed F, Chen J, Kumar V, Tian S, Lipp M, Lu TT Abstract Lymph node blood vessels play important roles in the support and trafficking of immune cells. The blood vasculature is a component of the vascular-stromal compartment that also includes the lymphatic vasculature and fibroblastic reticular cells (FRCs). During immune responses as lymph nodes swell, the blood vasculature undergoes a rapid proliferative growth that is initially dependent on CD11c(+) cells and vascular endothelial growth factor (VEGF) but is independent of lymphocytes. The lymphatic vasculature grows with similar kinetics and VEGF dependence, suggesting coregulation of blood and lymphatic vascular growth, but lymphatic growth has been shown to be B cell dependent. In this article, we show tha... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5361871 Wed, 26 Oct 2011 04:00:00 +0100 5361871 http://www.medworm.com/index.php?rid=5346115&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22021612%26dopt%3DAbstract Authors: Smolinska MJ, Page TH, Urbaniak AM, Mutch BE, Horwood NJ Abstract The TLRs play a key role in host defense against infection and injury, and mounting evidence suggests that these receptors may also play a role in diseases such autoimmunity, atherosclerosis, and cancer. Activation of TLRs on macrophages results in the production of multiple soluble mediators including the key inflammatory cytokines, TNF and IL-6. Thus, the intracellular signaling mechanism by which TLRs signal is a subject of great interest. As well as activating the NF-κB and MAPK pathways, TLR engagement leads to tyrosine kinase activation within minutes. Src family kinases (SFKs) are the largest nonreceptor tyrosine kinase family with nine members: Src, Hck, Lyn, Fyn, Fgr, Blk, Lck, Yes, and Ylk. The ro... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5346115 Fri, 21 Oct 2011 04:00:00 +0100 5346115 http://www.medworm.com/index.php?rid=5346114&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22021613%26dopt%3DAbstract In this study, we report that the inflammatory cytokine osteopontin (Opn) modulates memory CD8(+) T cell generation during influenza virus infection. Although Opn wild-type and Opn knockout (KO) mice had similar numbers of virus-specific effector CD8(+) T cells, virus-specific effector CD8(+) T cells generated in Opn KO mice showed low levels of T-bet expression and an increased memory precursor cell population compared with cells generated in Opn wild-type mice. This resulted in the persistently increased number of memory CD8(+) T cells in Opn KO mice. Studies with bone marrow-derived dendritic cells demonstrated that Opn deficiency in bone marrow-derived dendritic cells results in low levels of IL-12 production in response to the stimulation with influenza virus. Thus, we hypothesize tha... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5346114 Fri, 21 Oct 2011 04:00:00 +0100 5346114 http://www.medworm.com/index.php?rid=5346113&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22021614%26dopt%3DAbstract In this study, we show that the NKp44 receptor recognizes PCNA. Their interaction inhibits NK cell function through NKp44/ITIM. The physical interaction of NKp44 and PCNA is enabled by recruitment of target cell PCNA to the NK immunological synapse. We demonstrate that PCNA promotes cancer survival by immune evasion through inhibition of NKp44-mediated NK cell attack. PMID: 22021614 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5346113 Fri, 21 Oct 2011 04:00:00 +0100 5346113 http://www.medworm.com/index.php?rid=5346112&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22021615%26dopt%3DAbstract In this study, we demonstrate the role of an inhibitory interaction between T cell Ig and mucin domain-containing molecule 3 (Tim-3)-expressing CD8(+) T cells and galectin 9 (Gal-9) that could influence HSV-1 latency and reactivation. Accordingly, we show that most K(b)-gB tetramer-specific CD8(+) T cells in the TG of HSV-1-infected mice express Tim-3, a molecule that delivers negative signals to CD8(+) T cells upon engagement of its ligand Gal-9. Gal-9 was also upregulated in the TG when replicating virus was present as well during latency. This could set the stage for Gal-9/Tim-3 interaction, and this inhibitory interaction was responsible for reduced CD8(+) T cell effector function in wild-type mice. Additionally, TG cell cultures exposed to recombinant Gal-9 in the latent phase caused ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5346112 Fri, 21 Oct 2011 04:00:00 +0100 5346112 http://www.medworm.com/index.php?rid=5346111&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22021616%26dopt%3DAbstract Authors: McLeod IX, Zhou X, Li QJ, Wang F, He YW Abstract IL-7Rα-mediated signals are essential for naive T lymphocyte survival. Recent studies show that IL-7Rα is internalized and either recycled to cell surface or degraded. However, how the intracellular process of IL-7Rα trafficking is regulated is unclear. In this paper, we show that Vps34, the class III PI3K, plays a critical role in proper IL-7Rα intracellular trafficking. Mice lacking Vps34 in T lymphocytes had a severely reduced T lymphocyte compartment. Vps34-deficient T lymphocytes exhibit increased death and reduced IL-7Rα surface expression, although three major forms of autophagy remain intact. Intracellular IL-7Rα in normal T lymphocytes at steady state is trafficked through either early endosome/multivesicular ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5346111 Fri, 21 Oct 2011 04:00:00 +0100 5346111 http://www.medworm.com/index.php?rid=5346110&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22021617%26dopt%3DAbstract In this study, we sought to investigate whether the requirement for TOX was solely due to a role in ThPOK induction. In apparent support of this proposition, ThPOK upregulation and CD8 lineage repression were compromised in the absence of TOX, and enforced ThPOK expression could restore some CD4 development. However, these "rescued" CD4 cells were defective in many aspects of the CD4(+) T cell gene program, including expression of Id2, Foxo1, and endogenous Thpok, among others. Thus, TOX is necessary to establish the CD4(+) T cell lineage gene program, independent of its influence on ThPOK expression. PMID: 22021617 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5346110 Fri, 21 Oct 2011 04:00:00 +0100 5346110 http://www.medworm.com/index.php?rid=5346109&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22021618%26dopt%3DAbstract Authors: Mushaben EM, Kramer EL, Brandt EB, Khurana Hershey GK, Le Cras TD Abstract The mammalian target of rapamycin (mTOR) signaling pathway integrates environmental cues, promotes cell growth/differentiation, and regulates immune responses. Although inhibition of mTOR with rapamycin has potent immunosuppressive activity, mixed effects have been reported in OVA-induced models of allergic asthma. We investigated the impact of two rapamycin treatment protocols on the major characteristics of allergic asthma induced by the clinically relevant allergen, house dust mite (HDM). In protocol 1, BALB/c mice were exposed to 10 intranasal HDM doses over a period of 24 d and treated with rapamycin simultaneously during the sensitization/exposure period. In protocol 2, rapamycin was administe... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5346109 Fri, 21 Oct 2011 04:00:00 +0100 5346109 http://www.medworm.com/index.php?rid=5330808&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003197%26dopt%3DAbstract In this study, we demonstrate that lack of the inflammasome components ASC or NLRP3 that are centrally involved in caspase-1 activation decreases scores of clinical and histological disease severity as well as brain inflammation in murine pneumococcal meningitis. Using specific inhibitors (anakinra and rIL-18-binding protein), we further show that ASC- and NLRP3-dependent pathologic alterations are solely related to secretion of both IL-1β and IL-18. Moreover, using differentiated human THP-1 cells, we demonstrate that the pneumococcal pore-forming toxin pneumolysin is a key inducer of IL-1β expression and inflammasome activation upon pneumococcal challenge. The latter depends on the release of ATP, lysosomal destabilization (but not disruption), and cathepsin B activation. The in vivo i... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5330808 Fri, 14 Oct 2011 04:00:00 +0100 5330808 http://www.medworm.com/index.php?rid=5330804&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003198%26dopt%3DAbstract In this study, a detailed analysis of the B cell response to 2,4,6-trinitrophenol (TNP)-Ficoll was performed using normal mice. TNP-Ficoll delivered i.p. or i.v. induced rapid Ag-specific B-1b cell activation, expansion, isotype switching, and plasmablast/plasma cell differentiation. Ag-specific B-1b cell numbers peaked at day 5 and then gradually declined in the spleen but remained elevated in the peritoneal cavity beyond 40 d postimmunization. In addition to expressing CD43, CD44, and CD86, Ag-activated B-1b cells transiently expressed programmed cell death 1 (PD-1), which functionally suppressed BCR-induced B-1b cell in vitro proliferation when additional costimulatory signals were lacking. Inhibiting PD-1:PD-1 ligand interactions during TNP-Ficoll immunization significantly enhanced Ag... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5330804 Fri, 14 Oct 2011 04:00:00 +0100 5330804 http://www.medworm.com/index.php?rid=5330802&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003199%26dopt%3DAbstract Authors: Khader SA, Guglani L, Rangel-Moreno J, Gopal R, Fallert Junecko BA, Fountain JJ, Martino C, Pearl JE, Tighe M, Lin YY, Slight S, Kolls JK, Reinhart TA, Randall TD, Cooper AM Abstract IL-23 is required for the IL-17 response to infection with Mycobacterium tuberculosis, but is not required for the early control of bacterial growth. However, mice deficient for the p19 component of IL-23 (Il23a(-/-)) exhibit increased bacterial growth late in infection that is temporally associated with smaller B cell follicles in the lungs. Cxcl13 is required for B cell follicle formation and immunity during tuberculosis. The absence of IL-23 results in decreased expression of Cxcl13 within M. tuberculosis-induced lymphocyte follicles in the lungs, and this deficiency was associated with inc... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5330802 Fri, 14 Oct 2011 04:00:00 +0100 5330802 http://www.medworm.com/index.php?rid=5330800&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003200%26dopt%3DAbstract In this study, we report a functional role of miR-125b in macrophages. We found that miR-125b is enriched in macrophages compared with lymphoid cells and whole immune tissues. Enforced expression of miR-125b drives macrophages to adapt an activated morphology that is accompanied by increased costimulatory factor expression and elevated responsiveness to IFN-γ, whereas anti-miR-125b treatment decreases CD80 surface expression. To determine whether these alterations in cell signaling, gene expression, and morphology have functional consequences, we examined the ability of macrophages with enhanced miR-125b expression to present Ags and found that they better stimulate T cell activation than control macrophages. Further indicating increased function, these macrophages were more effective at ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5330800 Fri, 14 Oct 2011 04:00:00 +0100 5330800 http://www.medworm.com/index.php?rid=5330791&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003201%26dopt%3DAbstract Authors: Kearney DE, Wang W, Redmond HP, Wang JH Abstract Bacterial superantigens are Gram-positive exotoxins that induce proinflammatory cytokine release in vitro, cause lethal shock in vivo, and can be detected in the bloodstream of critically ill patients. They also have a powerful priming effect on the TLR4 agonist LPS. The aim of this study was to investigate the relationship between superantigens and the TLR2 agonist bacterial lipoprotein (BLP). Priming of human monocytes or PBMCs with superantigens significantly enhanced proinflammatory cytokine TNF-α and IL-6 release in response to BLP stimulation. The priming effect of superantigens could be blocked by inhibiting p38 MAPK during the priming phase as opposed to NF-κB or ERK inhibition. This was consistent with higher expr... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5330791 Fri, 14 Oct 2011 04:00:00 +0100 5330791 http://www.medworm.com/index.php?rid=5330780&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003202%26dopt%3DAbstract In this study, we report that cPLA(2) and its metabolite lipid mediators induced autophagy in the RAW246.7 macrophage cell line and in primary monocytes. IFN-γ-triggered autophagy involves activation of cPLA(2). Cysteinyl leukotrienes D(4) and E(4) and PGD(2) also induced these effects. The autophagy is independent of changes in mTOR or autophagic flux. cPLA(2) and lipid mediator-induced autophagy is ATG5 dependent. These data suggest that lipid mediators play a role in the regulation of autophagy, demonstrating a connection between the two seemingly separate innate immune responses, induction of autophagy and lipid mediator generation. PMID: 22003202 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5330780 Fri, 14 Oct 2011 04:00:00 +0100 5330780 http://www.medworm.com/index.php?rid=5330763&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003203%26dopt%3DAbstract Authors: Shainheit MG, Lasocki KW, Finger E, Larkin BM, Smith PM, Sharpe AH, Dinarello CA, Rutitzky LI, Stadecker MJ Abstract CBA/J mice infected with the helminth Schistosoma mansoni develop severe CD4 T cell-mediated hepatic granulomatous inflammation against parasite eggs associated with a robust Th17 cell response. We investigated the requisites for Th17 cell development using novel CD4 T cells expressing a transgenic TCR specific for the major Sm-p40 egg Ag, which produce IL-17 when stimulated with live schistosome eggs. Neutralization of IL-23 or blockade of the IL-1 receptor, but not IL-6 neutralization, abrogated egg-induced IL-17 secretion by transgenic T cells, whereas exogenous IL-23 or IL-1β reconstituted their ability to produce IL-17 when stimulated by syngeneic IL-1... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5330763 Fri, 14 Oct 2011 04:00:00 +0100 5330763 http://www.medworm.com/index.php?rid=5330762&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003204%26dopt%3DAbstract Authors: Steinwede K, Tempelhof O, Bolte K, Maus R, Bohling J, Ueberberg B, Länger F, Christman JW, Paton JC, Ask K, Maharaj S, Kolb M, Gauldie J, Welte T, Maus UA Abstract The growth factor GM-CSF has an important role in pulmonary surfactant metabolism and the regulation of antibacterial activities of lung sentinel cells. However, the potential of intra-alveolar GM-CSF to augment lung protective immunity against inhaled bacterial pathogens has not been defined in preclinical infection models. We hypothesized that transient overexpression of GM-CSF in the lungs of mice by adenoviral gene transfer (Ad-GM-CSF) would protect mice from subsequent lethal pneumococcal pneumonia. Our data show that intra-alveolar delivery of Ad-GM-CSF led to sustained increased pSTAT5 expression and PU.... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5330762 Fri, 14 Oct 2011 04:00:00 +0100 5330762 http://www.medworm.com/index.php?rid=5330761&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003205%26dopt%3DAbstract In this study, we examine the function of Klf3 in B cell development by studying B lymphopoiesis in a Klf3 knockout mouse model. We show that B cell differentiation is significantly impaired in the bone marrow, spleen, and peritoneal cavity of Klf3 null mice and confirm that the defects are cell autonomous. In the bone marrow, there is a reduction in immature B cells, whereas recirculating mature cells are noticeably increased. Immunohistology of the spleen reveals a poorly structured marginal zone (MZ) that may in part be caused by deregulation of adhesion molecules on MZ B cells. In the peritoneal cavity, there are significant defects in B1 B cell development. We also report that the loss of Klf3 in MZ B cells is associated with reduced BCR signaling strength and an impaired ability to r... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5330761 Fri, 14 Oct 2011 04:00:00 +0100 5330761 http://www.medworm.com/index.php?rid=5313540&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21987660%26dopt%3DAbstract Authors: Gobert AP, Asim M, Piazuelo MB, Verriere T, Scull BP, de Sablet T, Glumac A, Lewis ND, Correa P, Peek RM, Chaturvedi R, Wilson KT Abstract A strong cellular cross-talk exists between the pathogen Helicobacter pylori and high-output NO production. However, how NO and H. pylori interact to signal in gastric epithelial cells and modulate the innate immune response is unknown. We show that chemical or cellular sources of NO induce the anti-inflammatory effector heme oxygenase-1 (HO-1) in gastric epithelial cells through a pathway that requires NF-κB. However, H. pylori decreases NO-induced NF-κB activation, thereby inhibiting HO-1 expression. This inhibitory effect of H. pylori results from activation of the transcription factor heat shock factor-1 by the H. pylori virulence... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5313540 Mon, 10 Oct 2011 04:00:00 +0100 5313540 http://www.medworm.com/index.php?rid=5313539&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21987661%26dopt%3DAbstract Authors: Hao J, Dong S, Xia S, He W, Jia H, Zhang S, Wei J, O'Brien RL, Born WK, Wu Z, Wang P, Han J, Hong Z, Zhao L, Yin Z Abstract It has been demonstrated that the two main subsets of peripheral γδ T cells, Vγ1 and Vγ4, have divergent functions in many diseases models. Recently, we reported that Vγ4 γδ T cells played a protective role in tumor immunity through eomesodermin-controlled mechanisms. However, the precise roles of Vγ1 γδ T cells in tumor immunity, especially whether Vγ1 γδ T cells have any interaction with Vγ4 γδ T cells, remain unknown. We demonstrated in this paper that Vγ1 γδ T cells suppressed Vγ4 γδ T cell-mediated antitumor function both in vitro and in vivo, and this suppression was cell contact independent. Using neutralizing anti-IL-4 Ab... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5313539 Mon, 10 Oct 2011 04:00:00 +0100 5313539 http://www.medworm.com/index.php?rid=5313538&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21987662%26dopt%3DAbstract Authors: Obar JJ, Jellison ER, Sheridan BS, Blair DA, Pham QM, Zickovich JM, Lefrançois L Abstract In response to infection, CD8(+) T cells integrate multiple signals and undergo an exponential increase in cell numbers. Simultaneously, a dynamic differentiation process occurs, resulting in the formation of short-lived effector cells (SLECs; CD127(low)KLRG1(high)) and memory precursor effector cells (CD127(high)KLRG1(low)) from an early effector cell that is CD127(low)KLRG1(low) in phenotype. CD8(+) T cell differentiation during vesicular stomatitis virus infection differed significantly than during Listeria monocytogenes infection with a substantial reduction in early effector cell differentiation into SLECs. SLEC generation was dependent on Ebi3 expression. Furthermore, SLEC diff... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5313538 Mon, 10 Oct 2011 04:00:00 +0100 5313538 http://www.medworm.com/index.php?rid=5313537&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21987663%26dopt%3DAbstract In this report, using TCR δ(-/-) mice, we demonstrated a protective role of γδ T cells in Con A-induced hepatitis model. TCR δ(-/-) mice showed significantly decreased levels of IL-17A and IL-17F in the Con A-treated liver tissue, and reconstitution of TCR δ(-/-) mice with wild-type (Wt), but not IL-17A(-/-), γδ T cells significantly reduced hepatitis, strongly suggesting a critical role of IL-17A in mediating the protective effect of γδ T cells. Interestingly, only Vγ4, but not Vγ1, γδ T cells exerted such a protective effect. Furthermore, depletion of NKT cells in TCR δ(-/-) mice completely abolished hepatitis, and NKT cells from Con A-challenged liver tissues of TCR δ(-/-) mice expressed significantly higher amounts of proinflammatory cytokine IFN-γ than those from Wt mi... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5313537 Mon, 10 Oct 2011 04:00:00 +0100 5313537 http://www.medworm.com/index.php?rid=5247739&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934096%26dopt%3DAbstract Authors: Auchincloss H, Turka LA PMID: 21934096 [PubMed - in process] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5247739 Sat, 24 Sep 2011 01:56:47 +0100 5247739 http://www.medworm.com/index.php?rid=5247738&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934097%26dopt%3DAbstract Authors: Krummel MF, Allison JP PMID: 21934097 [PubMed - in process] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5247738 Sat, 24 Sep 2011 01:56:36 +0100 5247738 http://www.medworm.com/index.php?rid=5247737&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934098%26dopt%3DAbstract Authors: Walunas TL, Lenschow DJ, Bakker CY, Linsley PS, Freeman GJ, Green JM, Thompson CB, Bluestone JA PMID: 21934098 [PubMed - in process] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5247737 Sat, 24 Sep 2011 01:56:24 +0100 5247737 http://www.medworm.com/index.php?rid=5247736&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934099%26dopt%3DAbstract Authors: Campbell EL, Serhan CN, Colgan SP Abstract Mucosal surfaces function as selectively permeable barriers between the host and the outside world. Given their close proximity to microbial Ags, mucosal surfaces have evolved sophisticated mechanisms for maintaining homeostasis and preventing excessive acute inflammatory reactions. The role attributed to epithelial cells was historically limited to serving as a selective barrier; in recent years, numerous findings implicate an active role of the epithelium with proresolving mediators in the maintenance of immunological equilibrium. In this brief review, we highlight new evidence that the epithelium actively contributes to coordination and resolution of inflammation, principally through the generation of anti-inflammatory and pror... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5247736 Sat, 24 Sep 2011 01:56:13 +0100 5247736 http://www.medworm.com/index.php?rid=5233531&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21918184%26dopt%3DAbstract Authors: Weiskopf D, Yauch LE, Angelo MA, John DV, Greenbaum JA, Sidney J, Kolla RV, De Silva AD, de Silva AM, Grey H, Peters B, Shresta S, Sette A Abstract The frequency of dengue virus (DENV) infection has increased dramatically in the last few decades, and the lack of a vaccine has led to significant morbidity and mortality worldwide. To date, a convenient murine system to study human T cell responses to DENV has not been available. Mice transgenic for HLA are widely used to model human immune responses, and it has been shown that mouse-passaged DENV is able to replicate to significant levels in IFN-α/βR(-/-) mice. To cover a wide range of HLA phenotypes, we backcrossed IFN-α/βR(-/-) mice with HLA A*0201, A*0101, A*1101, B*0702, and DRB1*0101-transgenic mice. A DENV proteome... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5233531 Wed, 14 Sep 2011 04:00:00 +0100 5233531 http://www.medworm.com/index.php?rid=5233530&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21918185%26dopt%3DAbstract Authors: Ye F, Han L, Lu Q, Dong W, Chen Z, Shao H, Kaplan HJ, Li Q, Lu Q Abstract The TAM family of receptors (Tyro3, Axl, and Mertk) plays an important role in the negative regulation of response of dendritic cells (DCs) and macrophages to pathogenic stimuli, and mice lacking this receptor family develop spontaneous lupus-like systemic autoimmunity against a variety of tissues, including retina. To study the molecular mechanism underlying the TAM regulation of APC functions and subsequent effects on the induction of an autoimmune response against the eye, we examined CD4 T cell differentiation following retinal self-antigen immunization. CD4 T cells prepared from naive or interphotoreceptor retinoid-binding protein (IRBP)1-20-immunized Axl and Mertk double-knockout (dko) mice rea... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5233530 Wed, 14 Sep 2011 04:00:00 +0100 5233530 http://www.medworm.com/index.php?rid=5233529&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21918186%26dopt%3DAbstract In conclusion, encapsulation of GC does not only enhance their efficacy in the treatment of EAE but also alters their target cell specificity and their mode of action compared with free GCs. PMID: 21918186 [PubMed - as supplied by publisher] (Source: Journal of Immunology) Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5233529 Wed, 14 Sep 2011 04:00:00 +0100 5233529 http://www.medworm.com/index.php?rid=5233528&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21918187%26dopt%3DAbstract We report a transitional population of CD20(low/-)CD38(-) preplasmablasts along differentiation of human memory B cells into plasma cells in vitro. Preplasmablasts lack documented B cell or plasma cell (CD20, CD38, and CD138) markers, express CD30 and IL-6R, and secrete Igs at a weaker level than do plasmablasts or plasma cells. These preplasmablasts further differentiate into CD20(-)CD38(high)CD138(-) plasmablasts and then CD20(-)CD38(high)CD138(+) plasma cells. Preplasmablasts were fully characterized in terms of whole genome transcriptome profiling and phenotype. Preplasmablasts coexpress B and plasma cell transcription factors, but at a reduced level compared with B cells, plasmablasts, or plasma cells. They express the unspliced form of XBP1 mRNA mainly, whereas plasmablasts and plasm... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5233528 Wed, 14 Sep 2011 04:00:00 +0100 5233528 http://www.medworm.com/index.php?rid=5233527&cid=s_33860_3_f&fid=33860&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21918188%26dopt%3DAbstract In this study, we demonstrated that myeloid differentiation factor-2 (MD-2) is also tyrosine phosphorylated following LPS stimulation. LPS-induced tyrosine phosphorylation of MD-2 is specific; it is blocked by the tyrosine kinase inhibitor, herbimycin A, as well as by an inhibitor of endocytosis, cytochalasin D, suggesting that MD-2 phosphorylation occurs during trafficking of MD-2 and not on the cell surface. Furthermore, we identified two possible phospho-accepting tyrosine residues at positions 22 and 131. Mutant proteins in which these tyrosines were changed to phenylalanine had reduced phosphorylation and significantly diminished ability to activate NF-κB in response to LPS. In addition, MD-2 coprecipitated and colocalized with Lyn kinase, most likely in the endoplasmic reticulum. A ... Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5233527 Wed, 14 Sep 2011 04:00:00 +0100 5233527