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 'Trends in Immunology' source. Wed, 08 Feb 2012 06:43:03 +0100 http://www.medworm.com/index.php?rid=5642315&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22277903%26dopt%3DAbstract Authors: Ruffell B, Affara NI, Coussens LM Abstract Of the multiple unique stromal cell types common to solid tumors, tumor-associated macrophages (TAMs) are significant for fostering tumor progression. The protumor properties of TAMs derive from regulation of angiogenic programming, production of soluble mediators that support proliferation, survival and invasion of malignant cells, and direct and indirect suppression of cytotoxic T cell activity. These varied activities are dependent on the polarization state of TAMs that is regulated in part by local concentrations of cytokines and chemokines, as well as varied interactions of TAMs with normal and degraded components of the extracellular matrix. Targeting molecular pathways regulating TAM polarization holds great promise for ant... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5642315 Mon, 23 Jan 2012 05:00:00 +0100 5642315 http://www.medworm.com/index.php?rid=5578782&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227317%26dopt%3DAbstract Authors: Shi Y, Su J, Roberts AI, Shou P, Rabson AB, Ren G Abstract Mesenchymal stem cells (MSCs), also called multipotent mesenchymal stromal cells, exist in almost all tissues and are a key cell source for tissue repair and regeneration. Under pathological conditions, such as tissue injury, these cells are mobilized towards the site of damage. Tissue damage is usually accompanied by proinflammatory factors, produced by both innate and adaptive immune responses, to which MSCs are known to respond. Indeed, recent studies have shown that there are bidirectional interactions between MSCs and inflammatory cells, which determine the outcome of MSC-mediated tissue repair processes. Although many details of these interactions remain to be elucidated, we provide here a synthesis of the cu... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5578782 Fri, 06 Jan 2012 05:00:00 +0100 5578782 http://www.medworm.com/index.php?rid=5578783&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22222196%26dopt%3DAbstract Authors: O'Hara GA, Welten SP, Klenerman P, Arens R Abstract Typically, during viral infections, T cells encounter antigen, undergo proliferative expansion and ultimately contract into a pool of memory cells. However, after infection with cytomegalovirus, a ubiquitous β-herpesvirus, T cell populations specific for certain epitopes do not contract but instead are maintained and/or accumulate at high frequencies with a characteristic effector-memory phenotype. This feature has also been noted after other infections, for example, by parvoviruses. We discuss this so-called memory T cell inflation and the factors involved in this phenomenon. Also, we consider the potential therapeutic use of memory T cell inflation as a vaccine strategy and the associated implications for immune senesc... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5578783 Tue, 03 Jan 2012 05:00:00 +0100 5578783 http://www.medworm.com/index.php?rid=5561340&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209178%26dopt%3DAbstract Authors: King C, Sprent J Abstract The cellular networks that regulate humoral immune responses have been a focus of research over the past three decades. Studies have shown that inhibition of immune responses can be attributed to both suppressor T cells and B cells. More recently, T follicular helper (Tfh) cells have been identified as a target of immune regulation. Tfh cells are a subset of highly activated T helper cells specialized for providing cognate help to B cells during germinal center reactions. In this review, we describe emerging evidence for cellular networks that alter Tfh cell phenotype and function and regulate antibody production during the germinal center reaction. We discuss how these new findings influence our understanding of Tfh cells. PMID: 22209178 [Pub... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5561340 Wed, 28 Dec 2011 05:00:00 +0100 5561340 http://www.medworm.com/index.php?rid=5550724&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192781%26dopt%3DAbstract Authors: Martinez-Pomares L, Gordon S Abstract CD169(+) macrophages have fascinated immunologists because of their unique distribution in secondary lymphoid organs, redistribution upon immune activation and, lately, because of their contribution to antigen handling. Their association with B cell follicles prompted early studies on their involvement in B cell activation, and recent work has unveiled an unexpected role in facilitating activation of other lymphocyte subsets, such as invariant natural killer T (iNKT) cells. New data also argue that CD169(+) macrophages activate CD8 T cells in response to dead cell-associated antigens in lymph nodes and by transferring antigen to dendritic cells (DCs) in the spleen. Understanding the role of CD169(+) macrophages in the activation of acq... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5550724 Tue, 20 Dec 2011 05:00:00 +0100 5550724 http://www.medworm.com/index.php?rid=5536566&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177689%26dopt%3DAbstract Authors: Wojno ED, Hunter CA Abstract Interleukin (IL)-27 is a member of the IL-6 and IL-12 family composed of the IL-27p28 and Epstein-Barr virus-induced gene 3 (EBI3) subunits. Although IL-27 was originally identified as a proinflammatory factor, subsequent studies have revealed the pleiotropic nature of this cytokine. This review discusses recent work that has explored the effect of IL-27 on CD4(+) T cell subsets, including T regulatory type 1 (Tr-1) cells, T follicular helper cells (Tfhs), and forkhead box P3 (Foxp3)(+) T regulatory cells (Tregs). Additionally, we highlight studies that have identified a role for the IL-27p28 subunit as a cytokine receptor antagonist. Much of the recent work on IL-27 has been relevant to human disease states characterized by inappropriate or ex... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5536566 Wed, 14 Dec 2011 05:00:00 +0100 5536566 http://www.medworm.com/index.php?rid=5536565&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177690%26dopt%3DAbstract This article summarizes the similarities and differences between SAMHD1 and other HIV-1 restriction factors, while highlighting the new questions that are emerging about the crosstalk between restriction factors and innate immune responses. PMID: 22177690 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5536565 Wed, 14 Dec 2011 05:00:00 +0100 5536565 http://www.medworm.com/index.php?rid=5536567&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169337%26dopt%3DAbstract Authors: Croft M, Duan W, Choi H, Eun SY, Madireddi S, Mehta A Abstract The tumor necrosis factor (TNF) and TNF receptor superfamilies (TNFSF and TNFRSF) consist of approximately 50 membrane and soluble proteins that can modulate cellular function. Most of these molecules are expressed by or can target cells of the immune system, and they have a wide range of actions including promoting cellular differentiation, survival, and production of inflammatory cytokines and chemokines. Emerging data show that TNFSF ligand-receptor signaling pathways are active in inflammatory and autoimmune disease. Furthermore, several genetic polymorphisms in TNFSF and TNFRSF associate with susceptibility to developing disease. Here, we examine recent data regarding the potential of these molecules as ta... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5536567 Mon, 12 Dec 2011 05:00:00 +0100 5536567 http://www.medworm.com/index.php?rid=5536569&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22153930%26dopt%3DAbstract Authors: Koning JJ, Mebius RE Abstract Lymph nodes are strategically located throughout the body to allow lymphocytes to efficiently encounter their cognate antigen and become activated. The structure of the lymph nodes is such that B and T lymphocytes each have their own microdomain. This structure is provided by lymph node stromal cells, which also provide the lymphocytes with a scaffold upon which to migrate. Here, we discuss how stromal cells differentiate from mesenchymal precursor cells in response to the interaction with lymphocytes, while these stromal cells in turn provide necessary survival factors for the lymphocytes. We propose that during immune reactions, the interactions of stromal and immune cells are similarly important for controlling the expanding lymphocyte pool... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5536569 Tue, 06 Dec 2011 05:00:00 +0100 5536569 http://www.medworm.com/index.php?rid=5536568&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22153931%26dopt%3DAbstract Authors: Caminschi I, Shortman K Abstract Delivering antigens directly to dendritic cells (DCs) in situ, by injecting antigens coupled to antibodies specific for DC surface molecules, is a promising strategy for enhancing vaccine efficacy. Enhanced cytotoxic T cell responses are obtained if an adjuvant is co-administered to activate the DC. Such DC targeting is also effective at enhancing humoral immunity, via the generation of T follicular helper cells. Depending on the DC surface molecule targeted, antibody production can be enhanced even in the absence of adjuvants. In the case of Clec9A as the DC surface target, enhanced antibody production is a consequence of the DC-restricted expression of the target molecule. Few other cells absorb the antigen-antibody construct, therefore, ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5536568 Tue, 06 Dec 2011 05:00:00 +0100 5536568 http://www.medworm.com/index.php?rid=5475779&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22133865%26dopt%3DAbstract Authors: Oestreich KJ, Weinmann AS Abstract Lineage-defining transcription factors are responsible for activating the signature genes required for a given cell fate. They are also needed to repress the genetic programs associated with alternative lineage decisions. The T-box transcription factor T-bet is required for CD4(+) T helper 1 (Th1) cell differentiation. Numerous studies have explored the mechanisms by which T-bet activates the Th1 gene profile, but until recently not much was known about the mechanisms that T-bet utilizes to negatively regulate alternative T helper cell differentiation pathways such as the Th2 and Th17 fates. Here, we discuss new advances in the field that highlight the diverse mechanisms that T-bet employs to antagonize the gene programs for alternative T... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5475779 Tue, 29 Nov 2011 05:00:00 +0100 5475779 http://www.medworm.com/index.php?rid=5475780&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22094048%26dopt%3DAbstract Authors: Lowe DM, Redford PS, Wilkinson RJ, O'Garra A, Martineau AR Abstract Neutrophils are rapidly recruited to sites of mycobacterial infection, where they phagocytose bacilli. Whether neutrophils can kill mycobacteria in vivo probably depends on the tissue microenvironment, stage of infection, individual host, and infecting organism. The interaction of neutrophils with macrophages, as well as the downstream effects on T cell activity, could result in a range of outcomes from early clearance of infection to dissemination of viable bacteria together with an attenuated acquired immune response. In established disease, neutrophils accumulate in situations of high pathogen load or immunological dysfunction, and are likely to contribute to pathology. These activities may have clinica... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5475780 Tue, 15 Nov 2011 05:00:00 +0100 5475780 http://www.medworm.com/index.php?rid=5422756&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079120%26dopt%3DAbstract Authors: Agace WW, Persson EK Abstract CD103(+) dendritic cells (DCs) represent the major migratory DC population in the intestinal lamina propria and are believed to play an essential role in the initiation and regulation of mucosal adaptive immune responses. Small intestine (SI) CD103(+) DCs have an enhanced capacity to generate the vitamin A metabolite, retinoic acid, a property that underlies their ability to induce the gut homing receptors CC chemokine receptor 9 and α4β7 on responding T and B cells, and enhance forkhead box P3(+) T regulatory and IgA plasma cell differentiation in vitro. In this review, we discuss the environmental signals that appear to promote vitamin A metabolising activity in SI CD103(+) DCs in the steady state and thus which may contribute to driving t... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5422756 Fri, 11 Nov 2011 05:00:00 +0100 5422756 http://www.medworm.com/index.php?rid=5422758&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075206%26dopt%3DAbstract Authors: Procaccini C, Galgani M, De Rosa V, Matarese G Abstract Disorders such as obesity and type 2 diabetes have been linked to immune dysfunction, raising the possibility that metabolic alterations can be induced by or be a consequence of alterations in immunological tolerance. Here, we describe how intracellular metabolic signalling pathways can 'sense' host energy/nutritional status, and in response, modulate regulatory T (Treg) cell function. In particular, we focus on mammalian target of rapamycin (mTOR) signalling, and how stimuli such as nutrients and leptin activate mTOR in an oscillatory manner to determine Treg cell proliferation status. We propose that metabolic changes such as nutritional deprivation or overload could dictate the characteristics of the Treg cell comp... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5422758 Tue, 08 Nov 2011 05:00:00 +0100 5422758 http://www.medworm.com/index.php?rid=5422757&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075207%26dopt%3DAbstract Authors: Male V, Nisoli I, Gascoyne DM, Brady HJ Abstract Until recently, the basic leucine zipper transcription factor E4BP4 (also known as NFIL3) was of little interest to immunologists, being best known for its role in regulating circadian rhythm in chick pineal gland. However, characterisation of E4bp4(-/-) mice, independently generated in four different laboratories, has revealed roles for E4BP4 in diverse haematopoietic lineages. E4BP4 is essential for the development of NK cells and CD8α(+) conventional dendritic cells, and is also involved in macrophage activation, polarisation of CD4(+) T cell responses and B cell class switching to IgE. Here, we discuss the role of E4BP4 as a regulator of the immune response and highlight future questions for the field. PMID: 2207520... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5422757 Tue, 08 Nov 2011 05:00:00 +0100 5422757 http://www.medworm.com/index.php?rid=5422759&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056207%26dopt%3DAbstract Authors: Turchinovich G, Pennington DJ Abstract γδ cells have been conserved across ∼450 million years of evolution, from which they share the distinction, alongside αβ T cells and B cells, of forming antigen receptors by somatic gene recombination. However, much about these cells remains unclear. Indeed, although γδ cells display 'innate-like' characteristics exemplified by rapid tissue-localised responses to stress-associated stimuli, their huge capacity for T cell receptor (TCR)γδ diversity also suggests 'adaptive-like' potential. Clarity requires a better understanding of TCRγδ itself, not only through identification of TCR ligands, but also by correlating thymic TCRγδ signalling with commitment to γδ effector fates. Here, we propose that thymic TCRγδ-ligand e... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5422759 Thu, 03 Nov 2011 04:00:00 +0100 5422759 http://www.medworm.com/index.php?rid=5381741&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22030236%26dopt%3DAbstract Authors: Bennett CL, Chakraverty R Abstract Dendritic cells (DCs) prime and orchestrate naïve T cell immunity in lymphoid organs, but recent data also highlight the importance of DC-effector T cell interactions in tissues. These studies suggest that effector T cells require a second activating step in situ from tissue DCs to become fully competent for effector functions and/or proliferation and survival. DC stimulation of effector T cells within tissues has evolved as a mechanism to ensure that T cells are activated to their full potential only at the site of ongoing infection. Here, we propose that under conditions of uncontrolled inflammation and release of tissue antigens, the same DC-dependent checkpoint perpetuates a destructive response and immunopathology. PMID: 2203023... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5381741 Mon, 24 Oct 2011 04:00:00 +0100 5381741 http://www.medworm.com/index.php?rid=5381740&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22030237%26dopt%3DAbstract Authors: Pober JS, Tellides G Abstract Circulating T cells contact blood vessels either when they extravasate across the walls of microvessels into inflamed tissues or when they enter into the walls of larger vessels in inflammatory diseases such as atherosclerosis. The blood vessel wall is largely composed of three cell types: endothelial cells lining the entire vascular tree; pericytes supporting the endothelium of microvessels; and smooth muscle cells forming the bulk of large vessel walls. Each of these cell types interacts with and alters the behavior of infiltrating T cells in different ways, making these cells active participants in the processes of immune-mediated inflammation. In this review, we compare and contrast what is known about the nature of these interactions in h... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5381740 Mon, 24 Oct 2011 04:00:00 +0100 5381740 http://www.medworm.com/index.php?rid=5381739&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22030238%26dopt%3DAbstract Authors: Abeler-Dörner L, Swamy M, Williams G, Hayday AC, Bas A Abstract Butyrophilins (Btns) and butyrophilin-like (Btnl) molecules are emerging as novel regulators of immune responses in mice and humans. Several clues point to their probable importance: many of the genes are located within the MHC; they are structurally related to B7-co-stimulatory molecules; they are functionally implicated in T cell inhibition and in the modulation of epithelial cell-T cell interactions; and they are genetically associated with inflammatory diseases. Nonetheless, initial immersion into the current literature can uncover confusion over even basic information such as gene names and expression patterns, and seemingly conflicting data regarding the biological activities of different family members... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5381739 Mon, 24 Oct 2011 04:00:00 +0100 5381739 http://www.medworm.com/index.php?rid=5330697&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001488%26dopt%3DAbstract Authors: Tangye SG Abstract On describing the catastrophic effect of the plague during the Peloponnesian War, Greek historian Thucydides (c ∼450 BC) made the prescient observation that the "same man was never attacked twice - never at least fatally". This is probably the first description of the mammalian immune systems' remarkable ability to elicit a pathogen-specific response that potentially protects the host for its lifetime. This protection is largely mediated by plasma cells (PCs) that produce copious quantities of antibodies for extended periods of time, even after pathogen clearance. Here, I review the requirements for PC longevity in mice and humans, in particular the roles of survival niches in bone marrow and other tissues, and the "dialogue" between PCs and other cell... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5330697 Fri, 14 Oct 2011 04:00:00 +0100 5330697 http://www.medworm.com/index.php?rid=5330698&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22000665%26dopt%3DAbstract Authors: Baba Y, Kurosaki T Abstract In B cells, changes in intracellular concentration of Ca(2+) drive signal transduction to initiate changes in gene expression and various cellular events, including apoptosis and differentiation. B cell receptor engagement causes a transient Ca(2+) flux from the endoplasmic reticulum Ca(2+) store, followed by a continuous increase in intracellular Ca(2+) concentration, mainly resulting from store-operated Ca(2+) entry (SOCE). The recent identification of stromal interaction molecule (STIM) and Orai as essential components for SOCE has allowed researchers to probe further the role of Ca(2+) signals in B cell biology. Here, we summarize the B cell signaling pathways that lead to SOCE, the role of Ca(2+) signals in B cell regulatory function, and h... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5330698 Thu, 13 Oct 2011 04:00:00 +0100 5330698 http://www.medworm.com/index.php?rid=5330699&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21996313%26dopt%3DAbstract Authors: Parker D, Prince A Abstract The airway epithelium possesses many mechanisms to prevent bacterial infection. Not only does it provide a physical barrier, but it also acts as an extension of the immune system through the expression of innate immune receptors and corresponding effectors. One outcome of innate signaling by the epithelium is the production of type I interferons (IFNs), which have traditionally been associated with activation via viral and intracellular organisms. We discuss how three extracellular bacterial pathogens of the airway activate this intracellular signaling cascade through both surface components as well as via secretion systems, and the differing effects of type I IFN signaling on host defense of the respiratory tract. PMID: 21996313 [PubMed - a... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5330699 Tue, 11 Oct 2011 04:00:00 +0100 5330699 http://www.medworm.com/index.php?rid=5282005&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21962580%26dopt%3DAbstract Authors: Thompson EC PMID: 21962580 [PubMed - in process] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5282005 Sat, 01 Oct 2011 04:00:00 +0100 5282005 http://www.medworm.com/index.php?rid=5282004&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21962745%26dopt%3DAbstract Authors: Yewdell JW Abstract Defective ribosomal products (DRiPs) are a subset of rapidly degraded polypeptides that provide peptide ligands for major histocompatibility complex (MHC) class I molecules. Here, recent progress in understanding DRiP biogenesis is reviewed. These findings place DRiPs at the center of the MHC class I antigen processing pathway, linking immunosurveillance of viruses and tumors to mechanisms of specialized translation and cellular compartmentalization. DRiPs enable the immune system to rapidly detect alterations in cellular gene expression with great sensitivity. PMID: 21962745 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5282004 Thu, 29 Sep 2011 04:00:00 +0100 5282004 http://www.medworm.com/index.php?rid=5282003&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21962746%26dopt%3DAbstract Authors: Rubartelli A, Gattorno M, Netea MG, Dinarello CA Abstract Several inflammation-related processes, including inflammasome activation and interleukin (IL)-1β secretion, are dependent on redox signaling. However, the type of redox response involved as well as the relevant role of pro-oxidant and antioxidant events are matters of intense debate. By comparing leukemic myeloid cells, healthy monocytes and macrophages, as well as monocytes from patients carrying mutations in members of the Nod-like receptor (NLR) gene family, we have drawn a model that reconciles previous conflicting hypotheses. We propose that the redox state of resting inflammatory cells determines the type and extent of redox response to pattern recognition receptor stimulation, which in turn dictates the eff... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5282003 Wed, 28 Sep 2011 04:00:00 +0100 5282003 http://www.medworm.com/index.php?rid=5282006&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21958759%26dopt%3DAbstract Authors: Wilke CM, Bishop K, Fox D, Zou W Abstract Since their identification in 2005, T helper (Th)17 cells have been proposed to play important roles in several human diseases, including various autoimmune conditions, allergy, the development and progression of tumors, and the acceptance or rejection of transplanted organs and bone marrow. Focusing on human studies, here we review recent developments regarding Th17 biology and function in each of these fields. Th17 cells actively participate in the pathogenesis of autoimmune disease, allergy and transplantation rejection. Th17 cells contribute to protective antitumor immunity in human epithelial malignancy, whereas Th17-associated cytokines may also be associated with tumor initiation and growth in the context of chronic inflamma... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5282006 Tue, 27 Sep 2011 04:00:00 +0100 5282006 http://www.medworm.com/index.php?rid=5282008&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21940216%26dopt%3DAbstract Authors: Keating SE, Baran M, Bowie AG Abstract Type I interferon (IFN) induction is a crucial anti-pathogen response mediated by innate immune stimulation. Although it has been appreciated for some time that the presence of pathogen DNA within a cell leads to a type I IFN response, it is only in the past few years that some of the key signalling proteins and DNA sensors that regulate this response have been uncovered. Here, we review the nature of these DNA sensors, which includes a new family of pattern recognition receptors termed the AIM2-like receptors, and consider the implications of their discovery for understanding emerging principles of innate immune DNA sensing. Furthermore, we discuss how their discovery provides a rationale as to why accumulation of self-DNA mediates I... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5282008 Tue, 20 Sep 2011 04:00:00 +0100 5282008 http://www.medworm.com/index.php?rid=5282007&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21940217%26dopt%3DAbstract Authors: Kaur K, Sullivan M, Wilson PC Abstract Since its first administration in the 1940s, the influenza vaccine has provided tremendous relief against influenza infections. However, time has revealed the ultimate limit of the vaccine and the call for its reinvention has now come, just as we are beginning to appreciate the antibody immune responses vital in preventing infections. New strategies to design the influenza vaccine rely on selectively inducing broadly neutralizing antibodies that are specific for highly conserved viral epitopes. Such approaches take us away from the limited range of protection provided by current seasonal influenza vaccines and towards a future with a pan-influenza vaccine capable of providing universal strain coverage. PMID: 21940217 [PubMed - as ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5282007 Tue, 20 Sep 2011 04:00:00 +0100 5282007 http://www.medworm.com/index.php?rid=5233353&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21917522%26dopt%3DAbstract This article discusses some of the recent advances in our understanding of the mechanisms underlying mast cell recruitment. PMID: 21917522 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5233353 Mon, 12 Sep 2011 04:00:00 +0100 5233353 http://www.medworm.com/index.php?rid=5219497&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907000%26dopt%3DAbstract Authors: Houot R, Kohrt HE, Marabelle A, Levy R Abstract Monoclonal antibodies (mAbs) are in widespread use for the treatment of cancer. Their success as cancer therapeutics relies substantially on their ability to engage the immune system. Specifically, Fc-receptor-expressing immune cells mediate the killing of tumor cells by mAbs. Stimulation of these immune effector cells might therefore represent a promising strategy to enhance the therapeutic potential of mAbs. For instance, stimulation of natural killer cells, γδ T cells, macrophages, or dendritic cells can be used to enhance antibody-dependent cellular cytotoxicity, phagocytosis or even tumor vaccine effects. Here, we review several ways to improve the antitumor efficacy of mAbs by combining them with therapies that are di... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5219497 Thu, 08 Sep 2011 04:00:00 +0100 5219497 http://www.medworm.com/index.php?rid=5219498&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21890409%26dopt%3DAbstract Authors: Wallach D, Kovalenko A, Kang TB Abstract Necrosis, a form of death characterized by rupture of the cell membrane, is closely interlinked with inflammation. Cellular components released during necrotic death can trigger inflammation. Conversely, inflammation often yields tissue damage and, as a consequence, cell death. Which occurs first - necrosis or inflammation - in specific in vivo situations is currently difficult to tell. A way out of this 'chicken-and-egg' conundrum may be found via the recent finding that both necrotic cell death and inflammation can be initiated by a distinct set of signaling proteins, the 'necrosome', that includes receptor-interacting protein (RIP)1, RIP3 and caspase-8. Further clarifying the function of these signaling proteins should make it po... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5219498 Fri, 02 Sep 2011 04:00:00 +0100 5219498 http://www.medworm.com/index.php?rid=5219499&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889405%26dopt%3DAbstract Authors: Vacca P, Moretta L, Moretta A, Mingari MC Abstract During the early phases of pregnancy, natural killer (NK) cells are the predominant lymphoid cells in the human decidua. Here, rather than act as killers and/or drivers of inflammation, NK cells contribute to tissue building and remodeling and formation of new vessels due to the release of interleukin-8, vascular endothelial growth factor, stromal cell-derived factor-1 and interferon gamma-inducible protein-10. Here, we propose that the interaction of NK cells with CD14(+) myelomonocytic cells to promote induction of T regulatory cells plays a pivotal role in immunosuppression and tolerance towards the fetus allograft. Importantly, CD34(+) hematopoietic precursors are present in human decidua and may give rise to decidual ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5219499 Wed, 31 Aug 2011 04:00:00 +0100 5219499 http://www.medworm.com/index.php?rid=5157611&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21855411%26dopt%3DAbstract Authors: Roy AL, Sen R, Roeder RG Abstract Transcriptional regulation of eukaryotic protein-coding genes requires the participation of site-specific transcription factors that bind distal regulatory elements, as well as factors that, together with RNA polymerase II, form the basal transcription machinery at the core promoter. Gene regulation requires proper communication between promoters and enhancers, often over great distances. Therefore, it is important to understand the potentially inter-related transcription factor interactions at both of these elements. How this is achieved on tissue-specific genes, such as the immunoglobulin heavy chain (IgH) in B cells remains unclear. Here, we review known interactions at the Igh variable region (V(H)) promoters and present our perspectiv... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5157611 Wed, 17 Aug 2011 23:00:00 +0100 5157611 http://www.medworm.com/index.php?rid=5141879&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839681%26dopt%3DAbstract Authors: Williams MR, Azcutia V, Newton G, Alcaide P, Luscinskas FW Abstract Neutrophils are the all-terrain vehicle of the innate immune system because of their ability to gain entry into tissues and organs, and thus, play an essential role in host defense. Exactly how this marvel of nature works is still incompletely understood. In the past 2-3 years, new players and processes have been identified in the endothelial-leukocyte adhesion cascade. Novel signaling pathways have been discovered in both the endothelium and the neutrophils that regulate various steps in the recruitment process. This review focuses on these emerging pathways and the mechanisms that regulate neutrophil recruitment across endothelium. PMID: 21839681 [PubMed - as supplied by publisher] (Source: Trends in... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5141879 Thu, 11 Aug 2011 23:00:00 +0100 5141879 http://www.medworm.com/index.php?rid=5141878&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839682%26dopt%3DAbstract Authors: Sadik CD, Kim ND, Luster AD Abstract Neutrophils are pivotal effector cells of innate immunity. Their recruitment into peripheral tissues is indispensable for host defense. Given their destructive potential, neutrophil entry into tissue must be tightly regulated in vivo to avoid damage to the host. An array of chemically diverse chemoattractants is active on neutrophils and participates in recruitment. Neutrophil chemoattractants were thought redundant in the control of neutrophil recruitment into peripheral tissue, based on their often indistinguishable effects on neutrophils in vitro and their frequently overlapping patterns of expression at inflammatory sites in vivo. Recent data, however, suggest that neutrophil chemoattractants have unique functions in the recruitment... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5141878 Tue, 09 Aug 2011 23:00:00 +0100 5141878 http://www.medworm.com/index.php?rid=5141880&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21835696%26dopt%3DAbstract Authors: Koltsova EK, Ley K Abstract Atherosclerosis is an inflammatory disease of the arteries, which results in major morbidity and mortality. Immune cells initiate and sustain local inflammation. Here, we focus on how dendritic cell (DC)-mediated processes might be relevant to atherosclerosis. Although only small numbers of DCs are detected in healthy arteries, these numbers dramatically increase during atherosclerosis development. In the earliest fatty streaks, DCs are found next to the vascular endothelium. During plaque growth, new DCs are actively recruited, and their egress from the vessel wall is dampened. In the adventitia next to mature atherosclerotic lesions, tertiary lymphoid organs develop, which also contain DCs. Thus, DCs probably participate in all stages of ather... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5141880 Mon, 08 Aug 2011 23:00:00 +0100 5141880 http://www.medworm.com/index.php?rid=5141881&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820962%26dopt%3DAbstract Authors: Donnelly RP, Dickensheets H, O'Brien TR Abstract Interferon (IFN)-α, a type-I IFN, is widely used to treat chronic hepatitis C virus infection, but the broad expression of IFN-α receptors often leads to adverse reactions in many organs. Here, we examine IFN-λ, a type-III IFN, as a therapeutic alternative to IFN-α. Like IFN-α, IFN-λ also induces antiviral activity in hepatocytes, but might induce fewer adverse reactions because its receptor is largely restricted to cells of epithelial origin. We also discuss the recent discovery of single nucleotide polymorphisms (SNPs) near the human IFN-λ3 gene, IL28B, that correlate strongly with the ability to achieve a sustained virological response to therapy with pegylated IFN-α plus ribavirin in patients with chronic hepatit... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5141881 Wed, 03 Aug 2011 23:00:00 +0100 5141881 http://www.medworm.com/index.php?rid=5105706&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816673%26dopt%3DAbstract Authors: Scott CL, Aumeunier AM, Mowat AM CD103(+) dendritic cells (DCs) in the intestinal mucosa play a crucial role in tolerance to commensal bacteria and food antigens. These cells originate in the lamina propria (LP) and migrate to the mesenteric lymph nodes (MLNs), where they drive the differentiation of gut-homing FoxP3(+) regulatory T cells by producing retinoic acid from dietary vitamin A. Local 'conditioning' factors in the LP might also contribute to this tolerogenic profile of CD103(+) DCs. Considerably less is understood about the generation of active immunity or inflammation in the intestinal mucosa. This might require alterations in pre-existing CD103(+) DCs, arrival of new DCs, or the action of a distinct DC population. Here, we discuss our current knowledge of this as y... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5105706 Mon, 01 Aug 2011 23:00:00 +0100 5105706 http://www.medworm.com/index.php?rid=5105711&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782511%26dopt%3DAbstract Authors: Bratton DL, Henson PM Maintenance of circulating, functional neutrophils and their robust recruitment to tissues in response to injury and/or microbial infection are crucial for host defense. Equally important, although less well understood, are the processes for removal of these short-lived cells. Here, we review recent findings of novel neutrophil characteristics that determine removal. These neutrophil-derived signals, in turn, can shape the responses of other cells and surrounding tissues and promote a return to homeostasis. If not removed, dying neutrophils disintegrate and release phlogistic cargo that can further contribute to ongoing inflammation, tissue destruction, or autoimmunity. PMID: 21782511 [PubMed - in process] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5105711 Sun, 31 Jul 2011 23:00:00 +0100 5105711 http://www.medworm.com/index.php?rid=5105707&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802990%26dopt%3DAbstract Authors: Mazo IB, Massberg S, von Andrian UH Migration of hematopoietic stem cells (HSCs) is essential during embryonic development and throughout adult life. During embryogenesis, trafficking of HSCs is responsible for the sequential colonization of different hematopoietic organs by blood-producing cells. In adulthood, circulation of HSCs maintains homeostasis of the hematopoietic system and participates in innate immune responses. HSC trafficking is also crucial in clinical settings such as bone marrow (BM) and stem cell transplantation. This review provides an overview of the molecular and cellular signals that control and fine-tune trafficking of HSCs and hematopoietic progenitor cells in embryogenesis and during postnatal life. We also discuss the potential clinical utility of the... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5105707 Thu, 28 Jul 2011 23:00:00 +0100 5105707 http://www.medworm.com/index.php?rid=5105708&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21798806%26dopt%3DAbstract Authors: Strickland DH, Holt PG Asthma is a chronic disease of the airways, most commonly driven by immuno-inflammatory responses to ubiquitous airborne antigens. Epidemiological studies have shown that disease is initiated early in life when the immune and respiratory systems are functionally immature and less able to maintain homeostasis in the face of continuous antigen challenge. Here, we examine the cellular and molecular mechanisms that underlie initial aeroallergen sensitization and the ensuing regulation of secondary responses to inhaled allergens in the airway mucosa. In particular, we focus on how T-regulatory (Treg) cells influence early asthma initiation and the potential of Treg cells as therapeutic targets for drug development in asthma. PMID: 21798806 [PubMed - as su... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5105708 Tue, 26 Jul 2011 23:00:00 +0100 5105708 http://www.medworm.com/index.php?rid=5105709&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21783420%26dopt%3DAbstract Authors: Gregory LG, Lloyd CM House dust mites (HDM; Dermatophagoides sp.) are one of the commonest aeroallergens worldwide and up to 85% of asthmatics are typically HDM allergic. Allergenicity is associated both with the mites themselves and with ligands derived from mite-associated bacterial and fungal products. Murine models of allergic airways disease for asthma research have recently switched from the use of surrogate allergen ovalbumin together with adjuvant to use of the HDM extract. This has accelerated understanding of how adaptive and innate immunity generate downstream pathology. We review the myriad ways in which HDM allergic responses are orchestrated. Understanding the molecular pathways that elicit HDM-associated pathology is likely to reveal novel targets for therapeuti... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5105709 Wed, 20 Jul 2011 23:00:00 +0100 5105709 http://www.medworm.com/index.php?rid=5105710&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782512%26dopt%3DAbstract Authors: Ghoreschi K, Laurence A, Yang XP, Hirahara K, O'Shea JJ T helper (Th)17 cells have been proposed to represent a new CD4(+) T cell lineage that is important for host defense against fungi and extracellular bacteria, and the development of autoimmune diseases. Precisely how these cells arise has been the subject of some debate, with apparent species-specific differences in mice and humans. Here, we describe evolving views of Th17 specification, highlighting the contribution of transforming growth factor-β and the opposing roles of signal transducer and activator of transcription (STAT)3 and STAT5. Increasing evidence points to heterogeneity and inherent phenotypic instability in this subset. Ideally, better understanding of expression and action of key transcription factors and... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5105710 Tue, 19 Jul 2011 23:00:00 +0100 5105710 http://www.medworm.com/index.php?rid=5058693&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21775206%26dopt%3DAbstract Authors: Koch U, Radtke F T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy of thymocytes affecting preferentially children and adolescents. The disease is heterogeneous and characterized by a large set of chromosomal and genetic alterations that deregulate the growth of maturing thymocytes. The identification of activating point mutations in NOTCH1 in more then 50% of all T-ALL cases highlights the NOTCH1 cascade as a central player of T-ALL pathogenesis. In this review, we summarize and update more recent findings on the molecular mechanisms of T-ALL with a particular emphasis on the oncogenic properties of aberrant NOTCH1 signaling. PMID: 21775206 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5058693 Sun, 17 Jul 2011 23:00:00 +0100 5058693 http://www.medworm.com/index.php?rid=5058696&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21752713%26dopt%3DAbstract Authors: Scheller J, Chalaris A, Garbers C, Rose-John S A disintegrin and metalloproteinase 17 (ADAM17), also known as tumor necrosis factor-α converting enzyme (TACE), is a membrane-bound enzyme that cleaves cell surface proteins, such as cytokines (e.g. TNFα), cytokine receptors (e.g. IL-6R and TNF-R), ligands of ErbB (e.g. TGFα and amphiregulin) and adhesion proteins (e.g. L-selectin and ICAM-1). Here we examine how ectodomain shedding of these molecules can alter their biology and impact on immune and inflammatory responses and cancer development. Gene targeting of Adam17 is embryonic lethal, highlighting the importance of ectodomain shedding during development. Tissue-specific deletion, or hypomorphic knock-in, of Adam17 demonstrates an in vivo role for ADAM17 in controlling in... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5058696 Sun, 10 Jul 2011 23:00:00 +0100 5058696 http://www.medworm.com/index.php?rid=5058695&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21752714%26dopt%3DAbstract Authors: Liu Z, Davidson A B cell activating factor (BAFF) is a crucial survival factor for transitional and mature B cells, and is a promising therapeutic target for systemic lupus erythematosus (SLE). A BAFF inhibitor, belimumab, is the first new drug in 50 years to be approved for the treatment of SLE. However, the mechanism of action of this drug is not entirely clear. In this review we will focus on the role of the BAFF-APRIL signaling pathway in the selection of autoreactive B cells, and discuss whether altered selection is the mechanism for the therapeutic efficacy of BAFF inhibition in SLE. PMID: 21752714 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5058695 Sun, 10 Jul 2011 23:00:00 +0100 5058695 http://www.medworm.com/index.php?rid=5058694&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21752715%26dopt%3DAbstract Authors: Elliott JM, Yokoyama WM Natural killer (NK) cells, like B and T lymphocytes, are potent effector cells that are crucial for immunity to tumors and infections. These effector responses must be controlled to avoid inadvertent attack against normal self. Yet, the mechanisms that guide NK cell tolerance differ from those guiding T and B cell tolerance. Here, we discuss how NK cells are licensed by self-MHC class I molecules through their inhibitory receptors which results in NK cell functional competence to be triggered through their activation receptors. We discuss recent data with respect to issues related to licensing, thereby providing a framework for unifying concepts on NK cell education. PMID: 21752715 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5058694 Sun, 10 Jul 2011 23:00:00 +0100 5058694 http://www.medworm.com/index.php?rid=5011308&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21733753%26dopt%3DAbstract Authors: De Nardo D, Latz E A strong link between inflammation and metabolism is becoming increasingly evident. A number of recent landmark studies have implicated the activation of the NLRP3 inflammasome, an interleukin-1β family cytokine-activating protein complex, in a variety of metabolic diseases including obesity, atherosclerosis and type 2 diabetes. Here, we review these new developments and discuss their implications for a better understanding of inflammation in metabolic disease, and the prospects of targeting the NLRP3 inflammasome for therapeutic intervention. PMID: 21733753 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5011308 Sun, 03 Jul 2011 23:00:00 +0100 5011308 http://www.medworm.com/index.php?rid=5011290&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21733754%26dopt%3DAbstract Authors: Zanin-Zhorov A, Dustin ML, Blazar BR Protein kinase C (PKC)-θ regulates conventional effector T (Teff) cell function. Since this initial finding, it has become clear that the role of PKC-θ in T cells is complex. PKC-θ plays a central role in Teff cell activation and survival, and negatively regulates stability of the immunological synapse (IS). Recent studies demonstrated that PKC-θ is required for the development of natural CD4(+)Foxp3(+) regulatory T (Treg) cells, and mediates negative regulation of Treg cell function. Here, we examine the role of PKC-θ in the IS, evidence for its distinct localization in Treg cells and the therapeutic implications of inhibiting PKC-θ in Teff cells, to reduce effector function, and in Treg cells, to increase suppressor function, for th... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=5011290 Sun, 03 Jul 2011 23:00:00 +0100 5011290 http://www.medworm.com/index.php?rid=4962988&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21697012%26dopt%3DAbstract Authors: Willinger T, Rongvaux A, Strowig T, Manz MG, Flavell RA Human hemato-lymphoid-system mice hold great promise for modeling and studying important human diseases in vivo, and to enable vaccine testing. Until now, several major limitations have restricted the utility of human hemato-lymphoid-system mice in translational research. Recently, however, significant advances have been made in improving these mice, based on the delivery of human cytokines to create a better environment for human cells in the mouse host. In this review, we discuss the various approaches with a particular focus on improving human hemato-lymphoid-system mice by human cytokine knock-in gene replacement. PMID: 21697012 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4962988 Sun, 19 Jun 2011 23:00:00 +0100 4962988 http://www.medworm.com/index.php?rid=4962987&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21697013%26dopt%3DAbstract Authors: Sakuishi K, Jayaraman P, Behar SM, Anderson AC, Kuchroo VK T cell immunoglobulin-3 (Tim-3) has been identified as a marker of differentiated interferon-γ-producing CD4(+) T helper type 1 and CD8(+) T cytotoxic type 1 cells. The interaction of Tim-3 with its ligand, galectin-9 (Gal-9), induces cell death, and in vivo blockade of this interaction results in exacerbated autoimmunity and abrogation of tolerance in experimental models, establishing Tim-3 as a negative regulatory molecule. Recent studies have uncovered additional mechanisms by which Tim-3 negatively regulates T cell responses, such as promoting the development of CD8(+) T cell exhaustion and inducing expansion of myeloid-derived suppressor cells. In contrast to this inhibitory effect on T cells, Tim-3-Gal-9 interac... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4962987 Sun, 19 Jun 2011 23:00:00 +0100 4962987 http://www.medworm.com/index.php?rid=4962990&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664184%26dopt%3DAbstract Authors: Walzer T, Vivier E Natural killer (NK) cells are highly motile cells that patrol lymphoid and non-lymphoid organs, and are poised to react to infectious or other inflammatory situations. Several NK cell subsets equipped with different sets of chemotactic G-protein-coupled receptors, and which display distinct distribution across lymphoid and non-lymphoid organs, have been described. These receptors detect various guidance cues including sphingosine-1-phosphate and chemokines that orchestrate NK cell trafficking. Here, we highlight recent advances regarding the receptors involved in NK cell migration, with a focus on bone marrow egress, entry into activated lymph nodes, extravasation into inflamed tissues, and motility within lymph nodes or tumors. Understanding NK cell migrati... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4962990 Tue, 07 Jun 2011 23:00:00 +0100 4962990 http://www.medworm.com/index.php?rid=4962989&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664185%26dopt%3DAbstract Authors: Ingersoll MA, Platt AM, Potteaux S, Randolph GJ Environmental signals at the site of inflammation mediate rapid monocyte mobilization and dictate differentiation programs whereby these cells give rise to macrophages or dendritic cells. Monocytes participate in tissue healing, clearance of pathogens and dead cells, and initiation of adaptive immunity. However, recruited monocytes can also contribute to the pathogenesis of infection and chronic inflammatory disease, such as atherosclerosis. Here, we explore monocyte trafficking in the context of acute inflammation, relying predominantly on data from microbial infection models. These mechanisms will be compared to monocyte trafficking during chronic inflammation in experimental models of atherosclerosis. Recent developments sugge... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4962989 Tue, 07 Jun 2011 23:00:00 +0100 4962989 http://www.medworm.com/index.php?rid=4919985&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21636323%26dopt%3DAbstract Authors: Hori S Forkhead box P3 (Foxp3)(+) regulatory T (Treg) cells represent a distinct cell lineage that is committed to suppressive functions, whose stable differentiation state ensures the robustness of self-tolerance and immune homeostasis in a changing environment. Recent studies have challenged this notion and suggest that Treg cells retain developmental plasticity to be reprogrammed to Foxp3(-) helper T cells in response to extrinsic perturbations such as inflammation and lymphopenia. This issue of Treg cell plasticity, however, remains controversial because other recent reports argue against the plasticity phenomena. Here, I propose that the controversies can be resolved by considering the heterogeneity model of plasticity, which hypothesizes that the observed plasticity does... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4919985 Mon, 30 May 2011 23:00:00 +0100 4919985 http://www.medworm.com/index.php?rid=4919988&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21620768%26dopt%3DAbstract Authors: Bailey-Bucktrout SL, Bluestone JA Breakdown in self-tolerance is caused, in part, by loss of regulatory T (Treg) cells. Recently, a controversy has surfaced about whether Treg cells are overwhelmingly stable, or if they can be reprogrammed in inflammatory and autoimmune environments. Those in the instability camp have shown that a fraction of Treg cells lose forkhead box P3 protein and acquire effector arm activities. Instability is coupled with interleukin-2 insufficiency and the inflammatory milieu that promotes reprogramming. Here, we highlight the basic tenets of each viewpoint and discuss technical, biological and environmental differences in the models that might help yield a unifying hypothesis. Also considered is how Treg cell instability could link to development of a... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4919988 Wed, 25 May 2011 23:00:00 +0100 4919988 http://www.medworm.com/index.php?rid=4919990&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21616718%26dopt%3DAbstract Authors: Dalmas E, Clément K, Guerre-Millo M In obesity, chronic low-grade inflammation is thought to mediate the effects of increased adipose tissue mass on metabolic comorbidity. Of the different cell types that contribute to obesity-induced inflammation in adipose tissue, this review focuses on macrophages and their monocytes precursors. Mechanisms for monocyte recruitment to adipose tissue, and how both monocytes and macrophages are phenotypically modified in this environment in response to increasing fat mass, are considered. The versatile phenotype of adipose tissue macrophages might contribute not only to inflammatory and metabolic alterations, but could also help to maintain adipose tissue homeostasis in the setting of obesity. PMID: 21616718 [PubMed - as supplied by publi... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4919990 Tue, 24 May 2011 23:00:00 +0100 4919990 http://www.medworm.com/index.php?rid=4870662&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21612981%26dopt%3DAbstract Authors: Snelgrove RJ, Godlee A, Hussell T The lung is exposed to a myriad of innocuous antigens on a daily basis and must maintain a state of immune ignorance or tolerance to these harmless stimuli to retain pulmonary homeostasis and to prevent potentially fatal immunopathology. Here, we examine how, in the lower airways, resident cell populations contribute to the immune regulatory strategies that restrain inflammation. During influenza infection, these suppressive signals must be overcome to elicit a protective immune response that eliminates the virus. We also discuss how, after resolution of infection, the lung does not return to the original homeostatic state, and how the induced altered state can persist for long periods, which leaves the lung more susceptible to other infectiou... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4870662 Sun, 22 May 2011 23:00:00 +0100 4870662 http://www.medworm.com/index.php?rid=4870678&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21570914%26dopt%3DAbstract The objective is to provide a rationale for targeting (or not targeting) individual HDAC enzymes with inhibitors for future immune-related applications. PMID: 21570914 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4870678 Wed, 11 May 2011 23:00:00 +0100 4870678 http://www.medworm.com/index.php?rid=4870681&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21565554%26dopt%3DAbstract Authors: Rescigno M In the intestine, multiple interactions occur with the external world. Thus, the intestinal mucosal barrier has to tolerate millions of microorganisms that commonly inhabit the gut, degrade and absorb food, and establish tolerance or immunity, depending on the nature of the encountered antigens. Recent findings have highlighted that intestinal epithelial cells are not simply a barrier, but also are crucial for integrating these external and internal signals and for coordinating the ensuing immune response. Here, I review these findings and show how epithelial cells harmonize information that comes from inflammatory and non-inflammatory components of the microbiota to preserve intestinal homeostasis. If dysregulated, this immunomodulatory function of epithelial cells... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4870681 Tue, 10 May 2011 23:00:00 +0100 4870681 http://www.medworm.com/index.php?rid=4815546&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459674%26dopt%3DAbstract Authors: Le Bourhis L, Guerri L, Dusseaux M, Martin E, Soudais C, Lantz O Mucosal-associated invariant T (MAIT) cells are a population of T cells that display a semi-invariant T cell receptor (TCR) and are restricted by the evolutionarily conserved major histocompatibility complex related molecule, MR1. Here, we review recent knowledge of this T cell population. MAIT cells are abundant in human blood, gut and liver, and display an effector phenotype. They follow an atypical pathway of development and preferentially locate to peripheral tissues. Human and mouse MAIT cells react to bacterially infected cells in an MR1-dependent manner. They migrate to the infection site and can be protective in experimental infection models. MAIT cells secrete interferon-γ, and interleukin-17 under cert... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815546 Sat, 30 Apr 2011 23:00:00 +0100 4815546 http://www.medworm.com/index.php?rid=4815544&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21493141%26dopt%3DAbstract Authors: Klein L, Hinterberger M, von Rohrscheidt J, Aichinger M Promiscuous expression of 'peripheral' tissue-restricted antigens (TRAs) by medullary thymic epithelial cells (mTECs) is essential for central tolerance. Remarkably, the expression of individual TRAs varies among mTECs and is confined to a perplexingly small number of cells. To reconcile this with the ensuing robust state of tolerance, one might envisage that mTECs serve primarily as an antigen reservoir, whereas tolerogenic recognition of TRAs would ultimately require antigen uptake and presentation by dendritic cells (DCs). Here, we survey the evidence for this 'antigen-spreading' scenario and relate it to findings that document autonomous antigen-presentation by mTECs. We suggest that DC-dependent and autonomous tolero... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815544 Sat, 30 Apr 2011 23:00:00 +0100 4815544 http://www.medworm.com/index.php?rid=4815542&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21493143%26dopt%3DAbstract Authors: Zepp J, Wu L, Li X Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is widely used to dissect molecular mechanisms of MS and to develop new therapeutic strategies. The T helper 17 (Th17) subset of CD4 T cells plays a crucial role in the development of EAE. IL-17, a cytokine produced by Th17 cells, participates in EAE pathogenesis through induction of inflammatory gene expression in target cells. Recent work has shown that Act1, a U-box E3 ubiquitin ligase, is recruited to IL-17 receptor (IL-17R) upon IL-17 stimulation and is required for IL-17-mediated signaling. Here, we review the molecular and cellular mechanisms by which IL-17 and Act1-mediated signaling contribute t... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815542 Sat, 30 Apr 2011 23:00:00 +0100 4815542 http://www.medworm.com/index.php?rid=4815541&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21493144%26dopt%3DAbstract Authors: Stavnezer J Activation-induced cytidine deaminase (AID) instigates mutations and DNA breaks in Ig genes that undergo somatic hypermutation and class switch recombination during B cell activation in response to immunization and infection. This review discusses how AID expression and activity are regulated, including recent discoveries of AID-interacting proteins that might recruit AID to Ig genes, and allow it to target both DNA strands. Also discussed is the accumulating evidence that AID binds to, mutates, and creates breaks at numerous non-Ig sites in the genome, which initiates cell transformation and malignancies. PMID: 21493144 [PubMed - in process] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815541 Sat, 30 Apr 2011 23:00:00 +0100 4815541 http://www.medworm.com/index.php?rid=4815539&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21530402%26dopt%3DAbstract Authors: Axtell RC, Raman C, Steinman L Interferon (IFN)-β is the treatment most often prescribed for relapsing-remitting multiple sclerosis (RRMS). 30-50% of MS patients, however, do not respond to IFN-β. In some cases, IFN-β exacerbates MS, and it consistently worsens neuromyelitis optica (NMO). To eliminate unnecessary treatment for patients who are non-responsive to IFN-β, and to avoid possible harm, researchers are identifying biomarkers that predict treatment outcome before treatment is initiated. These biomarkers reveal insights into the mechanisms of disease. Recent discoveries on human samples from patients with RRMS, NMO, psoriasis, rheumatoid arthritis, systemic lupus erythematosus and ulcerative colitis, indicate that IFN-β is ineffective and might worsen clinical stat... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815539 Thu, 28 Apr 2011 23:00:00 +0100 4815539 http://www.medworm.com/index.php?rid=4815538&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531623%26dopt%3DAbstract Authors: Cope A, Le Friec G, Cardone J, Kemper C Control of IFN-γ-secreting T helper (Th) 1 cells prevents autoimmunity and immunopathology during infection. IL-10-mediated suppression of Th1 cells is achieved not only through IL-10 produced extrinsically, but also through a negative feedback loop that induces "intrinsic" IL-10 expression in cells also expressing IFN-γ, during Th1 lineage differentiation. Targeting this Th1 cell IFN-γ to IL-10 switching is a tantalising prospect for developing therapeutics for Th1-mediated diseases. In this review, the molecular pathways that regulate IFN-γ versus IL-10 expression in Th1 cells are examined, with focus on the role of complement regulator and T cell co-stimulatory molecule CD46, and also discussed are challenges and controversies in ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815538 Thu, 28 Apr 2011 23:00:00 +0100 4815538 http://www.medworm.com/index.php?rid=4815537&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531624%26dopt%3DAbstract Authors: Nagasawa T, Omatsu Y, Sugiyama T In the bone marrow, hematopoietic stem cells (HSCs) are maintained by special microenvironments, termed niches. The nature and function of these niches, however, remains unclear. HSCs are thought be in contact with bone-lining osteoblasts, but recent studies have suggested that only a small subpopulation of HSCs reside in this endosteal niche. By contrast, many HSCs are associated with the sinusoidal endothelium, which is referred to as the vascular niche. Recent data have suggested that primitive mesenchymal cells, including CXC chemokine ligand 12-abundant reticular cells and nestin-expressing cells act as HSC niches. Here, we review HSC niches, with an emphasis on the emerging role of reticular niches for maintaining HSCs in a proliferative ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815537 Thu, 28 Apr 2011 23:00:00 +0100 4815537 http://www.medworm.com/index.php?rid=4815536&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531625%26dopt%3DAbstract Authors: Mariño E, Silveira PA, Stolp J, Grey ST B cells play a pathogenic role as antigen-presenting cells and autoantibody secretors in the lead up to T cell-mediated autoimmune destruction of insulin-producing β cells in type 1 diabetes (T1D). This has led to significant interest in the use of B cell depletion therapies as a treatment for T1D. In this review, we compare results from five recent studies that used distinct B cell-depleting agents and protocols to successfully prevent and even reverse T1D in the non-obese diabetic (NOD) mouse model. We discuss how information gained from animal studies could be used to improve on the positive outcomes of a completed phase II clinical trial of the B cell-depleting drug rituximab in humans with recent-onset T1D. PMID: 21531625 [Pub... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815536 Thu, 28 Apr 2011 23:00:00 +0100 4815536 http://www.medworm.com/index.php?rid=4815540&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514223%26dopt%3DAbstract Authors: Cairo G, Recalcati S, Mantovani A, Locati M During inflammation, proinflammatory macrophages sequester iron as a well known bacteriostatic mechanism. Alternative activation of macrophages is linked to tissue repair, and during this process the expression pattern of genes important for iron homeostasis is distinct from that in proinflammatory macrophages. This leads to an increased capacity of the alternatively activated macrophages for heme uptake, via scavenger receptors, and for production of anti-inflammatory mediators via heme-oxygenase-dependent heme catabolism. Alternatively activated macrophages also release non-heme iron into tissues via ferroportin. Here, we propose that the iron-release-associated phenotype of alternatively activated macrophages significantly contrib... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815540 Tue, 19 Apr 2011 23:00:00 +0100 4815540 http://www.medworm.com/index.php?rid=4815543&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21493142%26dopt%3DAbstract Authors: Nawijn MC, Hackett TL, Postma DS, van Oosterhout AJ, Heijink IH The airway epithelium plays a role in immune regulation during environmental challenge, which is intertwined with its barrier function and capacity to limit submucosal access of environmental factors. In asthma, mucosal barrier function is often compromised, with disrupted expression of the adhesion molecule E-cadherin. Recent progress suggests that E-cadherin contributes to the structural and immunological function of airway epithelium, through the regulation of epithelial junctions, proliferation, differentiation, and production of growth factors and proinflammatory mediators that can modulate the immune response. Here, we discuss this novel role for E-cadherin in mediating the crucial immunological decision bet... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815543 Mon, 11 Apr 2011 23:00:00 +0100 4815543 http://www.medworm.com/index.php?rid=4815545&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21481636%26dopt%3DAbstract Authors: Witherden DA, Havran WL γδ T cells lie at the interface between innate and adaptive immunity, sharing features with both arms of the immune system. The vast majority of γδ T cells reside in epithelial layers of tissues such as skin, gut, lung, tongue and reproductive tract where they provide a first line of defense against environmental attack. The existence of epithelium-resident γδ T cells has been known for over 20 years but our understanding of the molecular events regulating development and function of these cells is incomplete. We review recent advances in the field, with particular emphasis on the γδ T cell population resident in mouse epidermis. These studies have enhanced our knowledge and understanding of the life cycle of this enigmatic population of cells. ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4815545 Thu, 07 Apr 2011 23:00:00 +0100 4815545 http://www.medworm.com/index.php?rid=4655028&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21435950%26dopt%3DAbstract Authors: Kim TS, Sun J, Braciale TJ The 2009 influenza pandemic highlighted the threat that type A influenza poses to human health. Thus, there is an urgency to understand the pathobiology of influenza infection and the contribution of the host immune response to virus elimination and the development of lung injury. This review focuses on the T cell arm of the adaptive host immune response to influenza. We assess recent developments in the understanding of how primary influenza virus-specific T cell responses are induced by antigen-presenting cells, the interaction of activated effector T cells with antigen-bearing cells in the infected lungs. Also examined is the contribution of influenza-specific effector T cells to the development and control of lung injury and inflammation during i... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4655028 Tue, 22 Mar 2011 00:00:00 +0100 4655028 http://www.medworm.com/index.php?rid=4655029&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21419699%26dopt%3DAbstract Authors: Cerutti A, Puga I, Cols M Mature B cells generate protective immunity by undergoing immunoglobulin (Ig) class switching and somatic hypermutation, two Ig gene-diversifying processes that usually require cognate interactions with T cells that express CD40 ligand. This T cell-dependent pathway provides immunological memory but is relatively slow to occur. Thus, it must be integrated with a faster, T cell-independent pathway for B cell activation through CD40 ligand-like molecules that are released by innate immune cells in response to microbial products. Here, we discuss recent advances in our understanding of the interplay between the innate immune system and B cells, particularly at the mucosal interface. We also review the role of innate signals in the regulation of Ig divers... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4655029 Wed, 16 Mar 2011 00:00:00 +0100 4655029 http://www.medworm.com/index.php?rid=4655030&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21411368%26dopt%3DAbstract Authors: Alter G, Altfeld M Accumulating data suggest that natural killer (NK) cells are involved not only in the innate antiviral response following infection, but also in shaping the quality of the adaptive immune response by modulating the functional properties of myeloid dendritic cells (DC) during the acute immune response to infection. In this role, NK cells ensure that only fully mature, immunogenic DCs gain access to inductive sites, where they might prime effective antiviral adaptive immune responses. However, increasing evidence now suggests that several aspects of this cross-talk between NK cells and DCs are compromised during HIV infection, potentially contributing to immune dysfunction. PMID: 21411368 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4655030 Mon, 14 Mar 2011 00:00:00 +0100 4655030 http://www.medworm.com/index.php?rid=4592936&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21388881%26dopt%3DAbstract Authors: Finetti F, Paccani SR, Rosenbaum J, Baldari CT The assembly and maintenance of primary cilia, which orchestrate signaling pathways centrally implicated in cell proliferation, differentiation and migration, are ensured by multimeric protein particles in a process known as intraflagellar transport (IFT). It has recently been demonstrated that a number of IFT components are expressed in hematopoietic cells, which have no cilia. Here, we summarize data for an unexpected role of IFT proteins in immune synapse assembly and intracellular membrane trafficking in T lymphocytes, and discuss the hypothesis that the immune synapse could represent the functional homolog of the primary cilium in these cells. PMID: 21388881 [PubMed - as supplied by publisher] (Source: Trends in Immunolog... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4592936 Fri, 11 Mar 2011 00:00:00 +0100 4592936 http://www.medworm.com/index.php?rid=4592935&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21388882%26dopt%3DAbstract Authors: Zaki MH, Lamkanfi M, Kanneganti TD Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis constitute a major health problem in developed countries. Moreover, IBD predisposes to the development of colorectal cancer. The intracellular NOD-like receptor Nlrp3 is rapidly emerging as a crucial regulator of intestinal homeostasis. This innate immune receptor mediates assembly of the inflammasome complex in the presence of microbial ligands, triggering caspase-1 activation and secretion of IL-1β and IL-18. Recent studies suggest that defective Nlrp3 inflammasome signaling in the gut contributes to IBD through increased permeability across the epithelial barrier and the induction of detrimental immune responses against invading commensals. Here, we review an... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4592935 Mon, 07 Mar 2011 00:00:00 +0100 4592935 http://www.medworm.com/index.php?rid=4592942&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21333600%26dopt%3DAbstract Authors: van de Veerdonk FL, Netea MG, Dinarello CA, Joosten LA Interleukin-1β (IL-1β) and IL-18 contribute to host defense against infection by augmenting antimicrobial properties of phagocytes and initiating Th1 and Th17 adaptive immune responses. Protein complexes called inflammasomes activate intracellular caspase-1 autocatalytically, which cleaves the inactive precursors of IL-1β and IL-18 into bioactive cytokines. In this review, we discuss the controversies regarding inflammasome activation and the role of the inflammasome during infection. We highlight alternative mechanisms for processing IL-1β and IL-18 during infection, which involve extracellular cleavage of the inactive cytokines by neutrophil-derived serine proteases or proteases released from cytotoxic T cells. P... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4592942 Tue, 01 Mar 2011 00:00:00 +0100 4592942 http://www.medworm.com/index.php?rid=4592938&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21371940%26dopt%3DAbstract Authors: Cox MA, Harrington LE, Zajac AJ The activation and differentiation of CD8 T cells is a necessary first step that endows these cells with the phenotypic and functional properties required for the control of intracellular pathogens. The induction of the CD8 T cell responses typically results in the development of a massive overall population of effector cells, comprising both highly functional but short-lived terminally differentiated cells, as well as a smaller subset of precursors that are predisposed to survive and transition into the memory T cell pool. In this review, we discuss how inflammatory cytokines and IL-2 bias the initial response towards short-lived effector generation, and also highlight the potential counterbalancing role of IL-21. PMID: 21371940 [PubMed - a... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4592938 Tue, 01 Mar 2011 00:00:00 +0100 4592938 http://www.medworm.com/index.php?rid=4592937&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21371941%26dopt%3DAbstract Authors: Perumal NB, Kaplan MH T helper (Th) cells are crucial for the development of immunity to infections and inflammatory disease. The acquisition of specific cytokine-secreting profiles, primed by the cytokine microenvironment, is required for effector function of Th cells. The most recent addition to the growing list of effector subsets are Th9 cells that secrete IL-9. In this review, we propose a model for the transcriptional regulation of the Il9 gene in IL-9-expressing T cells and the relatedness of this subset to other Th phenotypes. We suggest that transcription factors restricted to certain Th subsets and common among several subsets might play a role in the plasticity of Th9 cells. PMID: 21371941 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4592937 Tue, 01 Mar 2011 00:00:00 +0100 4592937 http://www.medworm.com/index.php?rid=4592939&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21354859%26dopt%3DAbstract Authors: Berry R, Chen Z, McCluskey J, Rossjohn J Expression of the pre-T cell receptor (pTCR) by immature thymocytes is crucial for T cell development. The pTCR comprises an invariant pre-Tα chain that pairs with a newly rearranged TCRβ chain and CD3 signaling components. Despite its similarity to the mature αβTCR, which binds to specific peptide-loaded major histocompatibility molecules, the pTCR functions in a ligand-independent manner. Precisely how pTCR functions autonomously has remained a source of intense debate. Recently, the structure of the extracellular domain of the pTCR has been determined, providing insight into the mechanism of pTCR autonomous signaling. In this review, we reflect on the current understanding of pTCR function and draw comparisons to the mechanisms e... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4592939 Fri, 25 Feb 2011 00:00:00 +0100 4592939 http://www.medworm.com/index.php?rid=4592940&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21334975%26dopt%3DAbstract Authors: Krysko DV, Agostinis P, Krysko O, Garg AD, Bachert C, Lambrecht BN, Vandenabeele P Cell death and injury often lead to release or exposure of intracellular molecules called damage-associated molecular patterns (DAMPs) or cell death-associated molecules. These molecules are recognized by the innate immune system by pattern recognition receptors - the same receptors that detect pathogen-associated molecular patterns, thus revealing similarities between pathogen-induced and non-infectious inflammatory responses. Many DAMPs are derived from the plasma membrane, nucleus, endoplasmic reticulum and cytosol. Recently, mitochondria have emerged as other organelles that function as a source of DAMPs. Here, we highlight the significance of mitochondrial DAMPs and discuss their contributi... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4592940 Fri, 18 Feb 2011 00:00:00 +0100 4592940 http://www.medworm.com/index.php?rid=4592941&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21334257%26dopt%3DAbstract Authors: Kerrigan AM, Brown GD The Syk-coupled C-type lectin receptor Dectin-1 was the first non-Toll like receptor described that could mediate its own intracellular signalling. It was initially identified as important for the innate recognition of and response to fungal pathogens but later studies revealed that it is also involved in triggering adaptive immune responses. It subsequently emerged that Dectin-1 is one of a number of spleen tyrosine kinase-coupled C-type lectin receptors that have been implicated not just in fungal immunity, but also in viral, mycobacterial and helminth infections. Here, we consider the ability of these receptors to trigger different aspects of immunity and highlight their emerging roles in a number of infection scenarios. PMID: 21334257 [PubMed - as... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4592941 Thu, 17 Feb 2011 00:00:00 +0100 4592941 http://www.medworm.com/index.php?rid=4479175&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21317039%26dopt%3DAbstract Authors: Witko-Sarsat V, Pederzoli-Ribeil M, Hirsh E, Sozzani S, Cassatella MA Recently, unexpected biological features of polymorphonuclear neutrophils have been revealed. In addition to their pivotal role in the defence against pathogens, neutrophils display a high degree of plasticity and contribute to control of adaptive immune responses. An emerging aspect of neutrophils is their ability to modulate their survival in response to both intrinsic and extrinsic factors. This review focuses on recent advances that have uncovered proliferating cell nuclear antigen (PCNA) and other cell cycle regulatory proteins as novel players regulating neutrophil survival. A better understanding of the mechanisms involved in neutrophil fate might pave the way for the identification of new anti-inflam... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4479175 Fri, 11 Feb 2011 00:00:00 +0100 4479175 http://www.medworm.com/index.php?rid=4479174&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21317040%26dopt%3DAbstract Authors: Guihot A, Bourgarit A, Carcelain G, Autran B The introduction of combined antiretroviral therapies (HAART) has reversed the fatal course of human immunodeficiency virus (HIV) infection. HAART controls virus production and, in most cases, allows the quantitative and functional immune defects caused by HIV to be reversed. Here, we review T cell homeostatic mechanisms that drive immune recovery. These homeostatic mechanisms, as well as differences in T cell antigen exposure, explain the distinct patterns of recovery for HIV-specific T cells versus T cells specific for other pathogens. Immune restoration during HAART can, however, have adverse effects. Immune restoration syndrome occurs in some patients as a result of successful but unbalanced immunity. PMID: 21317040 [PubMed ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4479174 Fri, 11 Feb 2011 00:00:00 +0100 4479174 http://www.medworm.com/index.php?rid=4479176&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21288770%26dopt%3DAbstract Authors: Lee YJ, Jameson SC, Hogquist KA A prominent population of innate CD8(+) T cells develops in the thymus of several gene-deficient mouse strains, including Itk, KLF2, CBP and Id3. These cells have the phenotype and function of memory CD8(+) T cells, without previous exposure to antigen. Surprisingly, the cytokine IL-4 plays a key role in their development. As this developmental mechanism was discovered, it came to light that innate CD8(+) T cells exist also in normal mice and in humans. In this review, we discuss how these cells develop, compare and contrast them to other CD8 memory cells, and discuss their potential physiological relevance. PMID: 21288770 [PubMed - in process] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4479176 Tue, 01 Feb 2011 00:00:00 +0100 4479176 http://www.medworm.com/index.php?rid=4414283&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21269878%26dopt%3DAbstract Authors: Gay NJ, Gangloff M, O'Neill LA Signaling by the toll-like receptor (TLR) and interleukin-1 receptor superfamily requires the adapter protein myeloid differentiation primary response protein 88 (MyD88). The recent determination of the structure of the so-called Myddosome provides us with new insights into the structural basis for innate immune signaling. Other information on the biochemistry and genetics of MyD88 and other adapters, such as MyDD adapter-like and TRIF-related adapter molecule, allows us to describe in some detail the signaling process activated by TLRs and provides new insights into the role these important proteins play in innate immunity. PMID: 21269878 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4414283 Mon, 24 Jan 2011 00:00:00 +0100 4414283 http://www.medworm.com/index.php?rid=4414299&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21251876%26dopt%3DAbstract Authors: Shaw MH, Kamada N, Warner N, Kim YG, Nuñez G The identification of several families of innate pattern recognition receptors has greatly enhanced our understanding of the host innate immune response against a variety of pathogens. One such family of innate receptors is the nucleotide-binding domain and leucine rich repeat containing receptors (NLRs). NOD2 has been characterized as a cytosolic sensor of bacteria peptidoglycan (PGN). For almost 10 years, NOD2 was assigned with the function of mediating the RICK- and nuclear factor-κB induced proinflammatory response triggered by PGN. Recent studies have extended the biological activity of NOD2 to include the induction of autophagy and antiviral responses, as well as mediating direct T cell activation. Here, we highlight and dis... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4414299 Tue, 18 Jan 2011 00:00:00 +0100 4414299 http://www.medworm.com/index.php?rid=4349921&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21227751%26dopt%3DAbstract Authors: van der Burg SH, Arens R, Melief CJ Persistent viral infections reflect a failure of the host's immune system to control infection, and in many cases, they are associated with the development of malignancies. So far, vaccines designed to boost viral immunity during chronic infection have not been successful. Infections with high-risk human papilloma viruses (e.g. HPV16) are acquired by a large segment of the population and persist in 5-10% of infected individuals, which causes the development of high-grade pre-malignant lesions. Recently we succeeded in causing regression of HPV16-induced disease in ∼50% of chronically infected patients by a novel therapeutic vaccine. Here, we summarize the parallels in immunity against HPV and other chronic viruses and discuss the general i... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4349921 Mon, 10 Jan 2011 00:00:00 +0100 4349921 http://www.medworm.com/index.php?rid=4349922&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216195%26dopt%3DAbstract Authors: Torrado E, Robinson RT, Cooper AM There has been a recent increase in our understanding of T cell responses during mycobacterial infection; however, we have not yet identified the protective mechanisms capable of mediating vaccine-induced protection in the lung. Novel approaches have allowed the determination of the kinetics and location of naïve T cell activation, as well as the factors that affect of antigen-specific T cell responses, and the balance between protective and immunopathological consequences during the chronic stages of infection. With an urgent need for new and more efficient vaccination strategies, the integration of these data will result in improved vaccine strategies. PMID: 21216195 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4349922 Thu, 06 Jan 2011 00:00:00 +0100 4349922 http://www.medworm.com/index.php?rid=4349923&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21190897%26dopt%3DAbstract Authors: Davis SJ, van der Merwe PA Exactly how ligand binding 'triggers' T cell receptor (TCR) phosphorylation is unclear. It has been proposed that ligand engagement by the TCR somehow activates the Src kinase Lck, which in turn phosphorylates the receptor. Recent data, however, suggest instead that a significant fraction of the Lck in resting T cells is already activated and that the proportion of active Lck does not change during the early stages of T cell activation. We argue that, caveats notwithstanding, these new observations offer support for the 'kinetic-segregation' model of TCR triggering, which involves spatial reorganization of signalling proteins upon ligand binding and requires a fraction of Lck to be active in resting T cells. PMID: 21190897 [PubMed - in process] (... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4349923 Sat, 01 Jan 2011 00:00:00 +0100 4349923 http://www.medworm.com/index.php?rid=4281666&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21168364%26dopt%3DAbstract Authors: Karasuyama H, Wada T, Yoshikawa S, Obata K Basophils, the least common type of granulocyte, have long been considered as minor effector cells in allergic responses because of their ability to release allergy-inducing chemical mediators such as histamine and leukotriene C4. However, it is unlikely that many animal species evolutionarily conserve basophils to only elicit allergic responses without any host-beneficial function. The study of basophils has been hampered by their rarity and difficult identification, as well as the lack of suitable animal models. Recent studies using novel analytical tools, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, have illuminated the crucial and nonredundant roles for basophils in protectiv... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4281666 Thu, 16 Dec 2010 00:00:00 +0100 4281666 http://www.medworm.com/index.php?rid=4281667&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21159556%26dopt%3DAbstract Authors: Harris N, Gause WC Similar T helper (Th)2-type immune responses are generated against different helminth parasites, but the mechanisms that initiate Th2 immunity, and the specific immune components that mediate protection against these parasites, can vary greatly. B cells are increasingly recognized as important during the Th2-type immune response to helminths, and B cell activation might be a target for effective vaccine development. Antibody production is a function of B cells during helminth infection and understanding how polyclonal and antigen-specific antibodies contribute should provide important insights into how protective immunity develops. In addition, B cells might also contribute to the host response against helminths through antibody-independent functions includi... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4281667 Mon, 13 Dec 2010 00:00:00 +0100 4281667 http://www.medworm.com/index.php?rid=4281669&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21147034%26dopt%3DAbstract Authors: Pang IK, Iwasaki A Influenza viruses infect a wide range of avian and mammalian host species including humans. Influenza viruses are a major cause of human respiratory infections and mortality. The innate immune system recognizes influenza viruses through multiple mechanisms. These include endosomal recognition through the Toll-like receptor 7 (TLR7) and cytosolic recognition through the retinoic acid inducible gene I (RIG-I). Recent studies also identified the role of nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) in innate detection of influenza viruses, leading to the activation of the inflammasomes. Here, we review the cellular and molecular mechanisms by which influenza virus infection leads to inflammasome activation, and discuss the consequences o... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4281669 Fri, 10 Dec 2010 00:00:00 +0100 4281669 http://www.medworm.com/index.php?rid=4281668&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21147035%26dopt%3DAbstract Authors: Fletcher AL, Malhotra D, Turley SJ Research into how self-reactive T cells are tolerized in lymph nodes has focused largely on dendritic cells (DCs). We now know that lymph node stromal cells (LNSC) are important mediators of deletional tolerance to peripheral tissue-restricted antigens (PTAs), which are constitutively expressed and presented by LNSCs. Of the major LNSC subsets, fibroblastic reticular cells and lymphatic endothelial cells are known to directly induce tolerance of responding naïve CD8 T cells. The biological outcome of this interaction fills a void otherwise not covered by DCs or thymic stromal cells. These findings, we suggest, necessitate a broadening of peripheral tolerance theory to include steady-state presentation of clinically relevant PTA to naïve CD8... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4281668 Fri, 10 Dec 2010 00:00:00 +0100 4281668 http://www.medworm.com/index.php?rid=4281670&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145789%26dopt%3DAbstract Authors: Quintana FJ, Cohen IR Heat shock proteins (HSPs) were initially discovered as participants in the cellular response to stress. It is now clear, however, that self and microbial HSPs also play an important role in the control of the immune response. Here, we focus on HSP60 and its interactions with both the innate and adaptive immune system in mammals. We also consider that circulating HSP60 and the quantities and specificities of serum antibodies to HSP60 provide a biomarker to monitor the immune status of the individual. Thus, the dual role of HSP60 as an immune modulator and a biomarker, provides an opportunity to modulate immunity for therapeutic purposes, and to monitor the immune response in health and disease. PMID: 21145789 [PubMed - as supplied by publisher] (Sourc... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4281670 Wed, 08 Dec 2010 00:00:00 +0100 4281670 http://www.medworm.com/index.php?rid=4253519&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21123113%26dopt%3DAbstract Authors: Clement CC, Rotzschke O, Santambrogio L Prenodal lymph is generated from the interstitial fluid that surrounds organs, and thus contains products of organ metabolism and catabolism. New proteomic analyses of lymph have identified proteins and peptides that are derived from capillary extravasation and tissue-specific proteins. Many of these peptides are detected at nanomolar concentrations in the lymph before passage through a regional lymph node. Before entering the node and once inside, proteins and processed peptides are filtered from the lymph by circulating immature dendritic cells (DCs) or non-activated nodal antigen-presenting cells (APCs) (macrophages, B cells and immature DCs). Here, we suggest that this process ensures organ-specific self-antigens are displayed to cir... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4253519 Mon, 29 Nov 2010 00:00:00 +0100 4253519 http://www.medworm.com/index.php?rid=4203395&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21106439%26dopt%3DAbstract Authors: Ouyang W, Li MO The forkhead box O (Foxo) family of transcription factors consists of the mammalian orthologs of the Caenorhabditis elegans longevity protein Daf-16, and has an evolutionarily conserved function in the regulation of nutrient sensing and stress responses. Recent studies have shown that Foxo proteins control expression of immune system-specific genes such as Il7ra in naïve T cells and Foxp3 in regulatory T cells, which are crucial regulators of T cell homeostasis and tolerance. These findings reveal that the ancient Foxo pathway has been co-opted to regulate highly specialized T cell activities. The Foxo pathway probably enables a diverse and self-tolerant population of T cells in the steady state, which is an important prerequisite for the establishment of a fu... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4203395 Mon, 22 Nov 2010 00:00:00 +0100 4203395 http://www.medworm.com/index.php?rid=4170214&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075684%26dopt%3DAbstract Authors: Kaplan DH PMID: 21075684 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4170214 Fri, 12 Nov 2010 00:00:00 +0100 4170214 http://www.medworm.com/index.php?rid=4170215&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071271%26dopt%3DAbstract Authors: Lewis J, Filler R, Smith DA, Golubets K, Girardi M The skin is at the forefront of environmental exposures, such as ultraviolet radiation and a myriad of chemicals, and is at risk for malignant transformation. The skin is a highly responsive immunological organ that contains a unique population of immature intraepidermal dendritic cells (DCs) called Langerhans cells (LCs). Although LCs show morphological and migratory changes in response to epidermal perturbation, and can function as antigen-presenting cells to activate T cells, their role in carcinogenesis is unknown. Here we review recent studies that have provided clues to the potential roles that LCs might play in the pathogenesis of skin cancer, beyond their stimulation or regulation of adaptive immunity. Understanding th... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4170215 Tue, 09 Nov 2010 00:00:00 +0100 4170215 http://www.medworm.com/index.php?rid=4170216&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21067974%26dopt%3DAbstract Authors: Condamine T, Gabrilovich DI Myeloid-derived suppressor cells (MDSCs) are one of the main cell populations responsible for regulating immune responses. MDSCs accumulate during tumor progression, autoimmunity, chronic infection and other pathological conditions, and can potently suppress T cell function. Recent studies have demonstrated the ability of MDSCs to modulate the activity of NK and myeloid cells and have implicated MDSCs in the induction of regulatory T cells. Here, we discuss recent findings that describe the molecular mechanisms that regulate the expansion and function of MDSCs, as well as recent attempts to use MDSCs in cell therapy for different pathologic conditions. PMID: 21067974 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4170216 Mon, 08 Nov 2010 00:00:00 +0100 4170216 http://www.medworm.com/index.php?rid=4140159&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21035396%26dopt%3DAbstract We describe a model in which the two best-characterized skin-resident DCs, langerhans cells (LCs) and Langerin(+) dermal DCs (dDCs) have distinct functions: Langerin(+) dDCs initiate and LCs suppress T cell responses. PMID: 21035396 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4140159 Wed, 27 Oct 2010 00:00:00 +0100 4140159 http://www.medworm.com/index.php?rid=4125489&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21030305%26dopt%3DAbstract Authors: Chorro L, Geissmann F Langerhans cells (LCs) are myeloid cells of the epidermis, featured in immunology textbooks as bone marrow-derived antigen-presenting dendritic cells (DCs). A new picture of LC origin, homeostasis and function has emerged, however, after genetic labelling and conditional cell ablation models in mice. LC precursors are recruited into the fetal epidermis, where they differentiate and proliferate in situ. In adults, LCs proliferate at steady state, and during inflammation, in response to signals from neighbouring cells. Here we review the experimental evidence that support either extra-embryonic yolk sac (YS) macrophages or hematopoietic stem cells (HSCs) as the origin of LCs. Beyond LC biology, we propose that YS and HSCs can contribute to the development o... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4125489 Tue, 26 Oct 2010 00:00:00 +0100 4125489 http://www.medworm.com/index.php?rid=4125488&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21030306%26dopt%3DAbstract Authors: de Jong MA, Geijtenbeek TB Langerhans cells (LCs) are at the frontline in defense against mucosal infections because they line the mucosal tissues and are ideally situated to intercept pathogens. Recent data suggest that LCs have an innate anti-HIV-1 function. LCs express the LC-specific C-type lectin Langerin that efficiently captures HIV-1, which prevents HIV-1 transmission. However, immune activation of LCs changes these protective cells into HIV-1-transmitting cells, which indicates that the antiviral function of LCs depends on several factors including co-infections. In this review, we discuss the dual role of LCs in innate defense against pathogens, with a focus on HIV-1 dissemination. PMID: 21030306 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4125488 Tue, 26 Oct 2010 00:00:00 +0100 4125488 http://www.medworm.com/index.php?rid=4078393&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951645%26dopt%3DAbstract Authors: Kobayashi Y, Watanabe T The ability to generate functional artificial lymphoid tissue to induce specific immunity at ectopic sites could offer a potential breakthrough for treatment of diseases such as cancer and severe infection using immunotherapy. Artificial lymphoid tissue could also offer an informative tool to study further lymphoid tissue development and function in vivo. Here, we review the process of secondary and tertiary lymphoid organization, of which an understanding is essential for artificial lymphoid tissue synthesis. Using this knowledge, we consider the combination of cell types, soluble factors and scaffold properties that will enable proper accumulation and organization of lymphocytes into tissue grafts. Recent success in in vivo induction of artificial lym... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4078393 Wed, 13 Oct 2010 23:00:00 +0100 4078393 http://www.medworm.com/index.php?rid=4078394&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951092%26dopt%3DAbstract Authors: Saenz SA, Noti M, Artis D The recent identification of previously unrecognized innate cell populations, termed natural helper cells (NHCs), multi-potent progenitor type 2 (MPP(type2)) cells, nuocytes, and innate type 2 helper (Ih2) cells has provided new insights into our understanding of the cellular mechanisms that lead to the development of CD4(+) Th2 cell-dependent immunity and/or inflammation at mucosal sites. In this review, we focus on the functional significance, similarities, and differences between NHCs, MPP(type2) cells, nuocytes and Ih2 cells. All four cell populations are activated by interleukin (IL)-25 and/or IL-33 and are capable of promoting Th2 cytokine responses. Collectively, the identification of these cell populations might illuminate ancient evolutionary... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4078394 Tue, 12 Oct 2010 23:00:00 +0100 4078394 http://www.medworm.com/index.php?rid=4045927&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20920889%26dopt%3DAbstract Authors: Valentini D, Gaseitsiwe S, Maeurer M PMID: 20920889 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4045927 Wed, 29 Sep 2010 23:00:00 +0100 4045927 http://www.medworm.com/index.php?rid=4027568&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20880743%26dopt%3DAbstract Authors: McAleer JP, Vella AT Toll-like receptor (TLR) adjuvants are capable of driving T cell immunity. The TLR4 agonist LPS activates antigen-presenting cells through myeloid differentiation primary response gene 88 (MyD88) and TIR domain-containing adaptor inducing interferon-beta (TRIF)-dependent signaling pathways, initiating CD4 T helper cell clonal expansion and differentiation. Lipopolysaccharide (LPS) supports the development of diverse T helper (Th) lineages depending on the tissue microenvironment. For instance, peripheral immunization with LPS drives Th1 priming in lymphoid tissue and Th17 priming in the gut. This could be due to commensal bacteria inducing Th17-stabilizing cytokines within the intestinal lamina propria. Here, we detail how the response to LPS stimulates CD... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4027568 Sun, 26 Sep 2010 23:00:00 +0100 4027568 http://www.medworm.com/index.php?rid=4013671&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20869317%26dopt%3DAbstract Authors: Blanchard N, Shastri N Within cells of their host, many bacteria and parasites inhabit specialized compartments, such as a modified phagosome for Mycobacterium tuberculosis or a parasitophorous vacuole for Toxoplasma gondii. These locations could exclude microbial material from entry into the MHC class I surveillance pathway. Remarkably, however, under these circumstances, cells can still signal the presence of invading pathogens to circulating CD8(+) T cells, which typically play a key role in protection against such intracellular organisms. Here, we review MHC I presentation pathways in various contexts, ranging from model antigens in non-infectious settings to pathogen-infected cells. We suggest that presentation of intracellular pathogens can be described as not just one, ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=4013671 Tue, 21 Sep 2010 23:00:00 +0100 4013671 http://www.medworm.com/index.php?rid=3982302&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20832361%26dopt%3DAbstract Authors: Hansen TH, Connolly JM, Gould KG, Fremont DH Major histocompatibility complex (MHC) class I molecules can be engineered as single chain trimers (SCTs) that sequentially incorporate all three subunits of the fully assembled proteins, namely peptide, β2 microglobulin, and heavy chain. SCTs have been made with many different MHC-peptide complexes and are used as novel diagnostic and therapeutic reagents, as well as probes for diverse biological questions. Here, we review the recent and diverse applications of SCTs. These applications include new approaches to enumerate disease-related T cells, DNA vaccines, eliciting responses to pre-assembled MHC-peptide complexes, and unique probes of lymphocyte development and activation. Future applications of SCTs will be driven by their ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3982302 Tue, 07 Sep 2010 23:00:00 +0100 3982302 http://www.medworm.com/index.php?rid=3982301&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20832362%26dopt%3DAbstract Authors: Hirsch I, Caux C, Hasan U, Bendriss-Vermare N, Olive D HIV-1, hepatitis B virus, hepatitis C virus, and human papillomavirus type 16 cause persistent infections that frequently precede cancer development. Virions of these viruses are weak inducers of interferon-α and impair Toll-like receptor (TLR)9 function. Loss of TLR9 responsiveness also occurs in tumors without viral etiology such as breast, ovary, and head and neck carcinomas. Recent reports have suggested that viruses and components of the tumor microenviroment interact with regulatory receptors on plasmacytoid dendritic cells (pDCs) to impair TLR7 and TLR9 signaling, and to downregulate TLR9 gene expression. The limited responsiveness of pDCs might contribute to reduced innate immune responses during chronic viral i... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3982301 Tue, 07 Sep 2010 23:00:00 +0100 3982301 http://www.medworm.com/index.php?rid=3958158&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20829112%26dopt%3DAbstract Authors: Janas ML, Turner M The progressive maturation of T cells is accompanied by their migration through the thymus, with each selection stage occurring in distinct microenvironments. Many specialized receptor-ligand pairs have been defined that drive T cell differentiation, but our understanding of the complex relationship between T cells and the thymic stroma is incomplete. Recent reports have identified a role for the chemokine stromal cell-derived factor 1α and its receptor CXC chemokine receptor 4 in β-selection. This review explores these findings in detail. PMID: 20829112 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3958158 Mon, 06 Sep 2010 23:00:00 +0100 3958158 http://www.medworm.com/index.php?rid=3958157&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20829113%26dopt%3DAbstract Authors: Björkström NK, Ljunggren HG, Sandberg JK Natural killer (NK) cells serve as a first line of defense against acute viral infections. Immunogenetic association data suggest that NK cells also influence the course of chronic viral infections, such as infections with HIV-1 and hepatitis C virus (HCV). Chronic stages of these infections have a negative impact on NK cell function and promote the appearance of phenotypically and functionally abnormal NK cells. In this paper, we summarize available data on CD56(neg) NK cells, an aberrant NK cell subset found in small numbers in healthy individuals and at elevated levels in individuals chronically infected with HIV-1 and HCV. We discuss current knowledge of CD56(neg) NK cells, with a particular emphasis on their accumulation duri... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3958157 Mon, 06 Sep 2010 23:00:00 +0100 3958157 http://www.medworm.com/index.php?rid=3958159&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20817556%26dopt%3DAbstract Authors: Kaminski DA, Randall TD Studies of immunity typically focus on understanding how hematopoietic cells interact within conventional secondary lymphoid tissues. However, immune reactions and their regulation occur in various environments within the body. Adipose tissue is one tissue that can influence and be influenced by adjacent and embedded lymphocytes. Despite the abundance and wide distribution of such tissue, and despite a growing obesity epidemic, studies of these interactions have been only marginally appreciated in the past. Here, we review advances in understanding of lymphoid structures within adipose tissue, the relationship between adipose tissue and adaptive immune function, and evidence for how this relationship contributes to obesity-associated diseases. PMID:... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3958159 Wed, 01 Sep 2010 23:00:00 +0100 3958159 http://www.medworm.com/index.php?rid=3934912&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20810318%26dopt%3DAbstract Authors: Yu D, Vinuesa CG Follicular helper T (Tfh) cells provide help to B cells and allow formation of long-lived antibody responses. Despite an improved understanding of the molecular program that drives Tfh cell formation, their definition remains elusive: neither follicular homing ability, Bcl-6 expression nor IL-21 secretion are exclusive properties of T cells that help B cells, and not all follicular T cells are B cell helpers. Indeed some follicular T cells appear to be suppressive. Furthermore, Tfh cells evolve during an immune response and B cells that have recently bound antigen, germinal center (GC) B cells and plasmablasts interact with phenotypically distinct Tfh cells. Here we propose that distinction between non-GC Tfh and GC Tfh cells might reconcile emerging controver... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3934912 Sun, 29 Aug 2010 23:00:00 +0100 3934912 http://www.medworm.com/index.php?rid=3885980&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20705510%26dopt%3DAbstract Authors: Netea MG, Maródi L Candida species are major causes of infections affecting either body surfaces or the deep tissues. Candida is a complex pathogen and the immune system uses various cells, cell surface receptors and signalling pathways to trigger an efficient host defence. Host-Candida interaction can result either in rapid elimination of the pathogen or the persistence of the pathogen in immunocompromised patients, leading to either chronic mucocutanous candidiasis or invasive candidiasis. Here, we discuss the molecular basis of receptor-mediated recognition and uptake of non-opsonized Candida and we describe the relative role of these receptors in initiating inflammation. In addition, the consequence of genetic defects in dectin-1 and dectin-1-mediated signalling and the... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3885980 Mon, 09 Aug 2010 23:00:00 +0100 3885980 http://www.medworm.com/index.php?rid=3855838&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20691634%26dopt%3DAbstract Authors: Eyerich S, Eyerich K, Cavani A, Schmidt-Weber C T helper (Th) cell subsets secrete cytokines that regulate other immune cells. Interleukin (IL)-17 and IL-22 belong to a new class of cytokines with predominant effects on epithelial cells. Thus, these cytokines are key molecules in several disease processes. IL-17 and IL-22 are released by leukocytes such as Th and natural killer cell populations. Both IL-17 and IL-22 induce an innate immune response in epithelial cells, but their functional spectra are generally distinct. IL-17 induces an inflammatory tissue response and is involved in the pathogenesis of several autoimmune diseases, whereas IL-22 is protective/regenerative. This review juxtaposes IL-17 and IL-22 and describes overlaps and differences regarding their cellular s... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3855838 Tue, 03 Aug 2010 23:00:00 +0100 3855838 http://www.medworm.com/index.php?rid=3855836&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20691635%26dopt%3DAbstract Authors: Ankeny DP, Popovich PG Emerging data indicate that traumatic injury to the brain or spinal cord activates B lymphocytes, culminating in the production of antibodies specific for antigens found within and outside the central nervous system (CNS). Here, we summarize what is known about the effects of CNS injury on B cells. We outline the potential mechanisms for CNS trauma-induced B cell activation and discuss the potential consequences of these injury-induced B cell responses. On the basis of recent data, we hypothesize that a subset of autoimmune B cell responses initiated by CNS injury are pathogenic and that targeted inhibition of B cells could improve recovery in cases of brain and spinal cord injury. PMID: 20691635 [PubMed - as supplied by publisher] (Source: Trends in... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3855836 Tue, 03 Aug 2010 23:00:00 +0100 3855836 http://www.medworm.com/index.php?rid=3827395&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20675191%26dopt%3DAbstract Authors: Zhu M, Brown NK, Fu YX Medullary thymic epithelial cells (mTECs) play a critical role in thymic negative selection of autoreactive thymocytes, especially for thymocytes specific for peripheral tissue-restricted self-antigens (TRA). Deficiency in lymphotoxin b receptor (LTbetaR) is associated with peripheral tissue inflammation, but whether this is caused by defective negative selection has been unclear; the significance of the LTbetaR pathway for negative selection is evident in some models but not others. Here, we revisit the data and clarify the role of LTbetaR in mTEC development and function and thymic TRA expression. These processes are discussed as potential mechanisms for LTbetaR-mediated control of negative selection. PMID: 20675191 [PubMed - as supplied by publish... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3827395 Thu, 29 Jul 2010 23:00:00 +0100 3827395 http://www.medworm.com/index.php?rid=3827396&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655806%26dopt%3DAbstract Authors: Burke S, Lakshmikanth T, Colucci F, Carbone E Natural killer (NK) cell-based immunotherapies treat hematopoietic malignancies, but are less effective against solid tumors. Here, we review recent data on NK cell recognition of melanoma at various stages of the disease and propose a combinatorial strategy to exploit fully the potential of NK cells. Depending on the stage of melanoma progression, NK cell-based therapies could be combined with pharmacological and T cell-based immunotherapies, to: (i) prevent lymph node metastases by redistributing cytotoxic NK cells; (ii) boost NK cell activity using chemotherapy to upregulate activating ligands on tumor cells; and (iii) target visceral metastases by transfer of autologous or allogeneic NK cells. PMID: 20655806 [PubMed - as su... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3827396 Wed, 21 Jul 2010 23:00:00 +0100 3827396 http://www.medworm.com/index.php?rid=3786486&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20650688%26dopt%3DAbstract Authors: Dong Z, Veillette A The signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) family of adaptors couples SLAM family receptors to activating intracellular signaling pathways that drive immune cell activation or differentiation. In the absence of SAP family adaptors, SLAM family receptors become inhibitory, possibly through coupling to the Src-homology-2-containing phosphatases. This "switch-of-function" of SLAM family receptors provides an explanation for the severe immune dysfunctions observed in humans with X-linked lymphoproliferative disease due to SAP deficiency, as well as in genetically engineered mice that lack SAP family adaptors. PMID: 20650688 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3786486 Mon, 19 Jul 2010 23:00:00 +0100 3786486 http://www.medworm.com/index.php?rid=3761931&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20634137%26dopt%3DAbstract Authors: Schlenner SM, Rodewald HR The long-standing model for hematopoiesis, which features a dichotomy into separate lymphoid and myeloid branches, predicts that progenitor T cells arise from a lymphocyte-restricted pathway. However, experiments that have detected myeloid potential in progenitor T cells have been reported as evidence to question this model. Mapping physiological differentiation pathways has now led to opposite conclusions, by showing that T cells and thymic myeloid cells have distinct origins and that, in vivo, T cell progenitors lack significant potential for myeloid lineages including dendritic cells. Here, we review the underlying experiments that have led to such fundamentally different conclusions. The current controversy might reflect a need to distinguish betw... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3761931 Mon, 12 Jul 2010 23:00:00 +0100 3761931 http://www.medworm.com/index.php?rid=3761932&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20630802%26dopt%3DAbstract Authors: Sivori S, Falco M, Moretta L, Moretta A Killer Ig-like receptors (KIRs) are human natural killer (NK) receptors that recognize allotypic determinants of human leukocyte antigen (HLA) class I. Inhibitory KIRs discriminate normal cells from tumour or virus-infected cells that have lost or reduced HLA class I expression. Donor NK cell "alloeffector" responses are exploited in haploidentical haematopoietic stem cell transplantation to treat leukaemia. NK cells also express several toll-like receptors (TLRs) that increase NK cell cytotoxicity and cytokine release in response to ligands. Surprisingly, KIR3DL2 binds the TLR ligand CpG-oligodexynucleotides, and together, they are co-internalized and translocated to TLR9-rich early endosomes. This novel KIR-associated function offers c... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3761932 Sun, 11 Jul 2010 23:00:00 +0100 3761932 http://www.medworm.com/index.php?rid=3751027&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20620114%26dopt%3DAbstract Authors: Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER Neutrophils play a key role in the elimination of pathogens. They are remarkably short-lived with a circulating half life of 6-8h and hence are produced at a rate of 5x10(10)-10x10(10) cells/day. Tight regulation of these cells is vital because they have significant histotoxic capacity and are widely implicated in tissue injury. This review outlines our current understanding of how neutrophils are released from the bone marrow; in particular, the role of the CXC chemokine receptor 4/stromal-derived factor 1 axis, the relative size and role of the freely circulating and marginated (i.e. slowly transiting) pools within the vascular compartment, and the events that result in the uptake and removal of circulating ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3751027 Wed, 07 Jul 2010 23:00:00 +0100 3751027 http://www.medworm.com/index.php?rid=3751028&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20619740%26dopt%3DAbstract Authors: Kern M, Popov A, Kurts C, Schultze JL, Knolle PA In lymphatic tissue, professional antigen-presenting cells (APCs) such as dendritic cells (DCs), mature after sensing microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs), and subsequently activate T cell immunity. Non-pathogenic MAMPs, derived for example from commensal bacteria, are delivered to the liver from the gastrointestinal tract via the portal vein. However, in contrast to splenic DCs, PRRs-expressing liver APCs induce T cell tolerance rather than immunity. This is explained partly by the distinct effects of PRRs on the maturation of liver APCs: these cells activate T cell immunity only when PRRs stimulation is accompanied by microbial infection through mechanisms that are not employed ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3751028 Tue, 06 Jul 2010 23:00:00 +0100 3751028 http://www.medworm.com/index.php?rid=3711384&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20579935%26dopt%3DAbstract Authors: Bae YS, Choi MK, Lee WJ Mucosal epithelia are in direct contact with microbes, which range from beneficial symbionts to pathogens. Accordingly, hosts must have a conflicting strategy to combat pathogens efficiently while tolerating symbionts. Recent progress has revealed that dual oxidase (DUOX) plays a key role in mucosal immunity in organisms that range from flies to humans. Information from the genetic model of Drosophila has advanced our understanding of the regulatory mechanism of DUOX and its role in mucosal immunity. Further investigations of DUOX regulation in response to symbiotic or non-symbiotic bacteria and the in vivo consequences in host physiology will give a novel insight into the microbe-controlling system of the mucosa. PMID: 20579935 [PubMed - as supplie... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3711384 Tue, 22 Jun 2010 23:00:00 +0100 3711384 http://www.medworm.com/index.php?rid=3711383&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20579936%26dopt%3DAbstract Authors: Sozzani S, Vermi W, Prete AD, Facchetti F Plasmacytoid dendritic cells (PDCs) represent a subset of circulating leukocytes characterized by the ability to release high levels of type I interferon (IFN). Under homeostatic conditions PDCs are confined to primary and secondary lymphoid organs. This is consistent with the restricted profile of functional chemotactic receptors expressed by circulating PDCs (i.e. CXCR4 and ChemR23). Accumulation of PDCs in non-lymphoid tissue is, however, observed in certain autoimmune diseases, allergic reactions and tumors. Indeed, PDCs are now considered to be involved in the pathogenesis of diseases characterized by a type I IFN-signature and are considered as a promising target for new intervention strategies. Here, current knowledge of the mol... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3711383 Tue, 22 Jun 2010 23:00:00 +0100 3711383 http://www.medworm.com/index.php?rid=3663285&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20542470%26dopt%3DAbstract Authors: Jeyanathan M, Heriazon A, Xing Z Protection against pulmonary tuberculosis (TB) by vaccination is often ascribed to the presence of TB-reactive T cells in the lung before infection. Challenging this view, new studies analyzing vaccine-induced T cells in various tissue compartments after parenteral immunization suggest a poor correlation between the presence of anti-TB T cells in the lung interstitium and spleen before Mycobacterium tuberculosis exposure and protection. In contrast, respiratory mucosal immunization leads to distribution of T cells not only in the lung interstitium and spleen, but also in the airway lumen, and the presence of these cells correlates well with protection. Furthermore, airway luminal recruitment of parenteral vaccine-induced T cells in peripheral t... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3663285 Thu, 10 Jun 2010 23:00:00 +0100 3663285 http://www.medworm.com/index.php?rid=3663284&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20542732%26dopt%3DAbstract LAT signaling pathology: an "autoimmune" condition without T cell self-reactivity. Trends Immunol. 2010 Jun 7; Authors: Roncagalli R, Mingueneau M, Grégoire C, Malissen M, Malissen B Partial loss-of-function mutations in several molecules involved in T-cell receptor (TCR) signaling result in inflammation and autoimmunity. How can mutations that reduce TCR signaling output, paradoxically lead to immune pathology? This review summarizes experiments demonstrating that mutations in the linker for activation of T cells (LAT) predispose toward aberrant T cell responses to antigen in the presence of normal thymic selection. In the absence of LAT, antigen-specific T cells give rise to self-perpetuating pro-inflammatory responses and induce the production of autoantibodies independen... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3663284 Sun, 06 Jun 2010 23:00:00 +0100 3663284 http://www.medworm.com/index.php?rid=3656191&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20538542%26dopt%3DAbstract Authors: Yang L, Pang Y, Moses HL Transforming growth factor beta (TGF-beta) plays an important role in tumor initiation and progression, functioning as both a suppressor and a promoter. The mechanisms underlying this dual role of TGF-beta remain unclear. TGF-beta exerts systemic immune suppression and inhibits host immunosurveillance. Neutralizing TGF-beta enhances CD8+ T-cell- and NK-cell-mediated anti-tumor immune responses. It also increases neutrophil-attracting chemokines resulting in recruitment and activation of neutrophils with an antitumor phenotype. In addition to its systemic effects, TGF-beta regulates infiltration of inflammatory/immune cells and cancer-associated fibroblasts in the tumor microenvironment causing direct changes in tumor cells. Understanding TGF-beta regul... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3656191 Mon, 31 May 2010 23:00:00 +0100 3656191 http://www.medworm.com/index.php?rid=3557051&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20452821%26dopt%3DAbstract Authors: Jaiswal S, Chao MP, Majeti R, Weissman IL Tumor immunosurveillance is a well-established mechanism for regulation of tumor growth. In this regard, most studies have focused on the role of T- and NK-cells as the critical immune effector cells. However, macrophages play a major role in the recognition and clearance of foreign, aged, and damaged cells. Macrophage phagocytosis is negatively regulated via the receptor SIRPalpha upon binding to CD47, a ubiquitously expressed protein. We recently showed that CD47 is up-regulated in myeloid leukemia and migrating hematopoietic progenitors, and that the level of protein expression correlates with the ability to evade phagocytosis. These results implicate macrophages in the immunosurveillance of hematopoietic cells and leukemias. The ab... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3557051 Thu, 06 May 2010 23:00:00 +0100 3557051 http://www.medworm.com/index.php?rid=3534235&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20434953%26dopt%3DAbstract Authors: Schäffler A, Schölmerich J The understanding of the role of adipose tissue has changed from a lipid storage organ to an endocrine and immunologically active organ. Here, we summarize the evidence for an important role of adipose tissue in innate immunity. The review focuses on the expression and function of Toll-like receptors (TLRs) in adipocytes and on the role of adipose tissue macrophages. The dual activation of TLR4 in adipocytes by lipopolysaccharide and fatty acids represents a molecular gate that connects innate immunity with metabolism. Dichotomic molecules derived from ancient precursor molecules control metabolism and immune function. Visceral adipose tissue is infiltrated by macrophages in obesity, and there is local crosstalk between these two types of cells... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3534235 Wed, 28 Apr 2010 23:00:00 +0100 3534235 http://www.medworm.com/index.php?rid=3441848&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20362509%26dopt%3DAbstract Authors: Via CS The parent-into-F1 model has led to important advances in our understanding of lupus. Here, we review the work in murine lupus that elucidated the role of T cells and supported the conclusion that the parent-into-F1 model of induced lupus compares favorably with de facto gold standard spontaneous models of lupus. Then we focus on recent work in parent-into-F1 mice, which has yielded novel insights into unresolved controversies, such as the role of apoptosis in the pathogenesis of lupus and lupus in patients receiving TNF blockade. Finally, the review considers the evidence that supports a potential role for CD8 T cells, both cytotoxic and memory cells, in mediating disease remission. PMID: 20362509 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3441848 Tue, 30 Mar 2010 23:00:00 +0100 3441848 http://www.medworm.com/index.php?rid=3435365&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20356792%26dopt%3DAbstract Authors: Vettermann C, Jäck HM The first step in establishing the antibody repertoire in humans and mice is the rearrangement of immunoglobulin heavy chain (HC) genes in early B lineage cells. These cells then assemble muHCs with surrogate light chains (SLC) into a pre-B cell receptor (pre-BCR). We propose that the pre-BCR has evolved from an ancient autoreactive BCR, since the SLC is an autoreactive entity that binds to the pre-BCR itself and to other self-antigens. Abrogation of autoreactivity in the SLC diminishes pre-BCR signaling and impairs the clonal expansion of pre-B cells producing functional muHCs. Since SLC expression is restricted to pre-B cells, the autoreactivity encoded by the pre-BCR can be utilized to pre-select the antibody repertoire, while simultaneously avoid... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3435365 Sun, 28 Mar 2010 23:00:00 +0100 3435365 http://www.medworm.com/index.php?rid=3435364&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20356793%26dopt%3DAbstract Authors: Dudakov JA, Khong DM, Boyd RL, Chidgey AP Most of the steps of lymphopoiesis have been elucidated but contentious issues remain, particularly regarding the identity and function of the earliest lymphoid progenitors that leave the bone marrow and seed the thymus. Hematopoiesis is effectively continuous throughout life, but there is a profound decline in immune function with increasing age, driven by thymus involution and severely curtailed B cell development. A key question is whether defects in bone marrow progenitors, such as reduced differentiation and repopulation potential, are the common denominator. While thymic involution temporally precedes overt HSC functional decline, a logical supposition is that the latter exacerbates the former. This review explores this possible ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3435364 Sun, 28 Mar 2010 23:00:00 +0100 3435364 http://www.medworm.com/index.php?rid=3312364&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20181527%26dopt%3DAbstract This article reviews the challenging questions regarding the link between PIAS3 and the intracellular signalling in immune cells. Some of the known functions of PIAS3 that potentially modulate key proteins in the immune system will also be discussed. PMID: 20181527 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3312364 Mon, 22 Feb 2010 00:00:00 +0100 3312364 http://www.medworm.com/index.php?rid=3312363&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20181528%26dopt%3DAbstract Authors: Parry RV, Ward SG Protein arginine methylation has emerged as a key regulator of signal transduction with an important role in T lymphocyte activation. The predominant methyl transferase PRMT-1 is highly expressed in T helper cells, and ligation of the T cell antigen and costimulatory receptors, induces arginine methylation on several cytoplasmic proteins. Global inhibition of methyl transferases can result in signaling defects in CD4 T cells and profound immunosuppression. Here we suggest that manipulating protein arginine methylation could be a feasible strategy to modulate T lymphocyte function, presenting a novel approach towards immunotherapy and the treatment of T cell-mediated disorders such as autoimmune disease and transplant rejection. PMID: 20181528 [PubMed - as... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3312363 Mon, 22 Feb 2010 00:00:00 +0100 3312363 http://www.medworm.com/index.php?rid=3312362&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20181529%26dopt%3DAbstract Authors: Hofmann J, Greter M, Du Pasquier L, Becher B A fundamental tenet of immunology is that adaptive immune responses are initiated in secondary lymphoid tissues. This dogma has been challenged by several recent reports. We discuss how successful T cell-mediated immunity can be initiated outside of such dedicated structures, whereas they are required for adaptive humoral immunity. This resembles an ancient immune pathway in the oldest cold-blooded vertebrates, which lack lymph nodes and sophisticated B-cell responses including optimal affinity maturation. The T-cell, however, has retained the capacity to recognize antigen in a lymph node-free environment. Besides bone marrow and lung, the liver is one organ that can potentially serve as a surrogate lymphoid organ and could represen... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3312362 Mon, 22 Feb 2010 00:00:00 +0100 3312362 http://www.medworm.com/index.php?rid=3303395&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176506%26dopt%3DAbstract Authors: Prechl J, Papp K, Erdei A Advances in protein microarray technology allow the generation of high content, reliable information about complex, multilevel protein interaction networks. Yet antigen arrays are used mostly only as devices for parallel immune assays describing multitudes of individual binding events. We propose here that the huge amount of immunological information hidden in the plasma of an individual could be better revealed by combining the characterization of antibody binding to target epitopes with improved estimation of effector functions triggered by these binding events. Furthermore, we could generate functional immune profiles characterizing general immune responsiveness of the individual by designing arrays incorporating epitope collections from diverse su... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3303395 Sat, 20 Feb 2010 00:00:00 +0100 3303395 http://www.medworm.com/index.php?rid=3291824&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20153253%26dopt%3DAbstract The objective herein is, therefore, to identify the many ways that aluminium chemistry contributes to the wide and versatile armoury of its adjuvants, such that future research might be guided towards a fuller understanding of their role in human vaccinations. PMID: 20153253 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3291824 Wed, 10 Feb 2010 00:00:00 +0100 3291824 http://www.medworm.com/index.php?rid=3291823&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20153254%26dopt%3DAbstract Authors: Hajishengallis G, Lambris JD The Toll-like receptors (TLRs) and complement are key innate defense systems that are triggered rapidly upon infection. Although both systems have been investigated primarily as separate entities, an emerging body of evidence indicates extensive crosstalk between complement and TLR signaling pathways. Analysis of these data suggests that the complement-TLR interplay reinforces innate immunity or regulates excessive inflammation, through synergistic or antagonistic interactions, respectively. However, the facility of complement and TLRs for communication is exploited by certain pathogens as a means to modify the host response in ways that favor the persistence of the pathogens. Further elucidation of regulatory links between complement and TLRs is e... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3291823 Wed, 10 Feb 2010 00:00:00 +0100 3291823 http://www.medworm.com/index.php?rid=3270157&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20149741%26dopt%3DAbstract Authors: Rehaume LM, Jouault T, Chamaillard M Candida albicans is a diploid fungus that colonizes the gastrointestinal tract asymptomatically in a large proportion of the human population, but can cause life-threatening conditions in immunocompromised patients. Recent immunological investigations have revealed the Nod-like receptor pyrin domain-containing protein 3 (NLRP3) to be a cytosolic surveillance mechanism against germinating Candida. These observations point to the idea of a molecular link between Candida and a spectrum of auto-inflammatory diseases. When excessive activation of NLRP3 occurs, it can confer resistance against disseminating Candida infection but might also cause NLRP3-associated periodic syndromes. Alternatively, we propose a pathophysiological model whereby a de... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3270157 Tue, 09 Feb 2010 00:00:00 +0100 3270157 http://www.medworm.com/index.php?rid=3270156&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20149742%26dopt%3DAbstract Authors: Selmi C, Gershwin ME PMID: 20149742 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3270156 Tue, 09 Feb 2010 00:00:00 +0100 3270156 http://www.medworm.com/index.php?rid=3270154&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20149744%26dopt%3DAbstract Authors: Greenspan NS Both affinity and specificity for ligands directly influence the functions of biological macromolecules. Some investigators assume that there is a consistent relationship between the affinity of a receptor molecule for its cognate ligand(s) and the specificity of that same receptor for cognate versus non-cognate ligands. However, analysis of the range of physical factors that account for changes in affinity, in any particular direction and to any particular degree, of a receptor for a cognate ligand suggests strongly that such factors can have disparate effects on the affinities of the receptor for different non-cognate ligands. Therefore, there can be no simple relationship between affinity and specificity as defined by relative binding of the receptor to cognate... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3270154 Tue, 09 Feb 2010 00:00:00 +0100 3270154 http://www.medworm.com/index.php?rid=3270155&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20149743%26dopt%3DAbstract Authors: Frossi B, Gri G, Tripodo C, Pucillo C Regulatory cells can mould the fate of the immune response by direct suppression of specific subsets of effector cells, or by redirecting effectors against invading pathogens and infected or neoplastic cells. These functions have been classically, although not exclusively, ascribed to different subsets of T cells. Recently, mast cells have been shown to regulate physiological and pathological immune responses, and thus to act at the interface between innate and adaptive immunity assuming different functions and behaviors at discrete stages of the immune response. Here, we focus on these poorly defined, and sometimes apparently conflicting, functions of mast cells. PMID: 20149743 [PubMed - as supplied by publisher] (Source: Trends in Im... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3270155 Mon, 08 Feb 2010 00:00:00 +0100 3270155 http://www.medworm.com/index.php?rid=3221174&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20106721%26dopt%3DAbstract Authors: Wick G, Backovic A, Rabensteiner E, Plank N, Schwendtner C, Sgonc R Fibrosis is an important health problem, and its pathogenetic principles are still largely unknown. It can develop either spontaneously, or, more frequently, as a consequence of various underlying diseases. Irrespective of the primary cause, however, fibrotic tissue is always infiltrated by mononuclear immune cells. In most instances the reason for the attraction of these cells to fibrotic tissue and their proliferation remains to be determined; however their cytokine profile shows clear-cut proinflammatory and profibrotic characteristics. In this review, we discuss the innate and adaptive immune reactions associated with the development of fibrosis and the molecular basis of the profibrotic mechanisms taking ... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3221174 Mon, 25 Jan 2010 00:00:00 +0100 3221174 http://www.medworm.com/index.php?rid=3197969&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20089450%26dopt%3DAbstract Authors: Ahlers JD, Belyakov IM CD8(+) cytotoxic T lymphocyte (CTL) responses are crucial in establishing the control of persistent virus infections. Population studies of HIV-1-infected individuals suggest that CD8(+) CTL responses targeting epitopes that take the greatest toll on virus replication are instrumental in immune control. A major question for vaccine design is whether incorporating epitopes responsible for controlling a persistent virus will translate into protection from natural infection or serve solely as a fail-safe mechanism to prevent overt disease in infected individuals. Here, we discuss qualitative parameters of the CD8(+) CTL response and mechanisms operative in the control of persistent virus infections and suggest new strategies for design and delivery of HIV v... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3197969 Mon, 18 Jan 2010 00:00:00 +0100 3197969 http://www.medworm.com/index.php?rid=3189619&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20083434%26dopt%3DAbstract Authors: Berg PA PMID: 20083434 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3189619 Sat, 16 Jan 2010 00:00:00 +0100 3189619 http://www.medworm.com/index.php?rid=3189620&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20080446%26dopt%3DAbstract Authors: Pigatto PD, Guzzi G PMID: 20080446 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3189620 Fri, 15 Jan 2010 00:00:00 +0100 3189620 http://www.medworm.com/index.php?rid=3164707&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20060781%26dopt%3DAbstract Authors: Maddur MS, Kaveri SV, Bayry J Recent reports demonstrate that basophils act as antigen presenting cells to drive Th2 and IgE responses against protease and protein allergens and helminth parasites. Through MHC class II-dependent cognate interactions with CD4(+) T cells in the context of co-stimulatory molecules, and through secretion of IL-4, IL-13 and thymic stromal lymphopoietin, basophils drive antigen-specific Th2 responses. These results have uncovered previously unknown functions of basophils, and should aid in designing novel therapeutic strategies for asthma and allergic conditions. PMID: 20060781 [PubMed - as supplied by publisher] (Source: Trends in Immunology) Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3164707 Thu, 07 Jan 2010 00:00:00 +0100 3164707 http://www.medworm.com/index.php?rid=3156704&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20056484%26dopt%3DAbstract Authors: Finney OC, Riley EM, Walther M T cell-mediated inflammatory immune responses contribute to both the clearance and pathology of malaria infections; the host's ability to down-regulate inflammation once parasitemia is controlled is crucial to avoid immune-mediated pathology but remains poorly understood. Various regulatory populations of T lymphocytes can modulate inflammatory immune responses and there has been considerable recent interest in the potential for regulatory T cells to modify the outcome of both murine and human malaria infections. Here, we review these studies, focussing in particular on recent studies in humans, propose a model by which different regulatory T cell populations might contribute to the control of inflammation at different stages of infection and dis... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3156704 Tue, 05 Jan 2010 00:00:00 +0100 3156704 http://www.medworm.com/index.php?rid=3125381&cid=s_36142_3_f&fid=36142&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20036798%26dopt%3DAbstract Authors: Figdor CG, van Spriel AB Fungal pattern-recognition receptors (F-PRRs), including C-type lectins, Toll-like receptors, scavenger receptors and Fc/complement receptors, are crucial for inducing anti-fungal immune responses by antigen-presenting cells. The recent identification of specific F-PRR interactions with tetraspanins has shed new light on the functioning of F-PRRs in the cell membrane and subsequent downstream signaling. Tetraspanins are small four-transmembrane proteins that can assemble immune receptors and signaling molecules into functional membrane microdomains. Here, we discuss the implications of this novel type of interaction between F-PRRs and tetraspanins in different subsets of antigen-presenting cells. We postulate that upon fungal binding tetraspanins modul... Trends in Immunology journals http://www.medworm.com/rss/comments.php?id=3125381 Fri, 25 Dec 2009 00:00:00 +0100 3125381