Latest Articles Include:
- From the editors
- Nature Reviews Immunology 10(3):153 (2010)
The bone marrow could be considered to be the immune system's safe house — being a secure location, suitable for lying low and staying out of harms way. Indeed, haematopoietic stem cells (HSCs) can safely lie dormant in specialized bone marrow niches, being aroused from their slumber to replenish blood cells only in times of need. - Thymocyte development: Cytokines have the casting vote
- Nature Reviews Immunology 10(3):154 (2010)
Signals through the T cell receptor (TCR) are crucial for the positive selection of double-positive (DP) thymocytes and for the differentiation of CD4+ T cells. Far less is known about how CD8+ T cell lineage specification occurs; this study indicates that although TCR signalling sets the stage for the differentiation of CD8+ T cells, signalling by cytokines such as interleukin-7 (IL-7) is the deciding factor. - T cells: TH2 cells have mixed loyalty
- Nature Reviews Immunology 10(3):155 (2010)
T helper 1 (TH1) and TH2 cells express unique sets of transcription factors and cytokines and are thought to be mutually exclusive subsets, with opposing immunological functions. Now, a recent paper in Immunity has shown that interferons (IFNs) can induce TH2 cells to adopt a stable intermediate phenotype that is characterized by the expression of both TH1- and TH2-type signature molecules. - In brief: Autoimmunity, Immune tolerance, Dendritic cells
- Nature Reviews Immunology 10(3):155 (2010)
March 2010 Vol 10 No 3 * Research Highlights * Reviews * Perspectives * Previous About the cover From the editors p153 | doi:10.1038/nri2741 Research Highlights Thymocyte development: Cytokines have the casting vote | PDF (150 KB) p154 | doi:10.1038/nri2732 CD8+ lineage specification requires cytokine but not TCR signalling. T cells: TH2 cells have mixed loyalty | PDF (246 KB) p155 | doi:10.1038/nri2733 Virus-induced IFNs cause TH2 cells to gain TH1-type functions. In brief Autoimmunity | Immune tolerance | Dendritic cells | PDF (173 KB) p155 | doi:10.1038/nri2740 Innate immunity: FOXO protects hungry flies | PDF (224 KB) p156 | doi:10.1038/nri2731 FOXO regulates AMP expression in response to starvation and disrupted insulin signalling. Autoimmunity: Platelets make bones ache | PDF (182 KB) p156 | doi:10.1038/nri2734 Platelet-derived microparticles express IL-1 and promote joint inflammation. Vaccine Watch Strategic variety | PDF (184 KB) p156 | doi:10.1038/nri2736 Innate immunity: A NOD to neutrophils | PDF (214 KB) p157 | doi:10.1038/nri2739 Peptidoglycan from the gut microbiota enhances systemic innate immune function. B cells: Direct hit by IL-21 | PDF (199 KB) p158 | doi:10.1038/nri2737 IL-21 receptor signalling by B cells prolongs germinal centre response. Tumour immunology: Antibodies lend support to tumours | PDF (214 KB) p158 | doi:10.1038/nri2738 Antibody binding to activating FcγRs establishes a pro-tumour environment Reviews Immune adaptations that maintain homeostasis with the intestinal microbiota Lora V. Hooper & Andrew J. Macpherson p159 | doi:10.1038/nri2710 Although the vast numbers of commensal organisms that reside in the human gut are essential for health, they pose a continuous threat of invasion. The intestinal immune system has evolved unique immunological adaptations that help to maintain intestinal homeostasis. * Abstract * Full Text * PDF (764 KB) The regulation of IL-10 production by immune cells Margarida Saraiva & Anne O'Garra p170 | doi:10.1038/nri2711 The anti-inflammatory cytokine interleukin-10 (IL-10) has a central role in limiting inflammatory responses to protect against excessive tissue damage. Recent evidence suggests that many types of immune cell can produce IL-10, but how is its transcription regulated in these different cell types? * Abstract * Full Text * PDF (511 KB) WASP: a key immunological multitasker Adrian J. Thrasher & Siobhan O. Burns p182 | doi:10.1038/nri2724 As a key regulator of the actin cytoskeleton, Wiskott–Aldrich syndrome protein (WASP) is involved in diverse immune responses, including leukocyte migration and activation. This Review describes how various mutations in mice and humans have led us to a greater appreciation of the many immunological functions of WASP. * Abstract * Full Text * PDF (470 KB) Organization of immunological memory by bone marrow stroma Koji Tokoyoda, Anja E. Hauser, Toshinori Nakayama & Andreas Radbruch p193 | doi:10.1038/nri2727 How are memory cells maintained? In this Review, the authors discuss the emerging role of mesenchymal stromal cells — which organize defined numbers of dedicated survival niches for different types of memory lymphocytes — in the maintenance of immunological memory. * Abstract * Full Text * PDF (365 KB) Perspectives Opinion Awakening dormant haematopoietic stem cells Andreas Trumpp, Marieke Essers & Anne Wilson p201 | doi:10.1038/nri2726 Haematopoietic stem cells (HSCs) can reside as dormant cells in endosteal niches in the bone marrow, where they are resistant to certain types of chemotherapy. In this article, the authors suggest that by first awakening dormant HSCs to become actively self-renewing cells, this resistance to chemotherapy could be overcome. * Abstract * Full Text * PDF (1,857 KB) Opinion NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Jurg Tschopp & Kate Schroder p210 | doi:10.1038/nri2725 This Opinion article discusses the evidence for and the limitations of the three main models of inflammasome activation. The authors propose that the production of reactive oxygen species might be a common factor downstream of many types of inflammasome activator. * Abstract * Full Text * PDF (592 KB) Erratum: Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function Maria T. Abreu p215 | doi:10.1038/nri2728 * Full Text * PDF (458 KB) - Innate immunity: FOXO protects hungry flies
- Nature Reviews Immunology 10(3):156 (2010)
Chromogranin A is an autoantigen in type 1 diabetes Stadinksi , B. D.et al. Nature Immunol.7 Feb 2010 (doi: 10.1038/ni.1844) - Autoimmunity: Platelets make bones ache
- Nature Reviews Immunology 10(3):156 (2010)
The immune and metabolic systems are closely integrated and evolutionarily conserved, and several pathways and transcription factors have been described that are central to this integration. Now, the transcription factor forkhead box O (FOXO), which has an important role in regulating metabolism, has been shown to be essential for the expression of antimicrobial peptides (AMPs) in response to starvation and disrupted insulin signalling in the fruit fly, Drosophila melanogaster. - Strategic variety
- Nature Reviews Immunology 10(3):156 (2010)
Platelets have well-described functions in haemostasis and blood clotting, but only recently have immunologists begun to appreciate the contribution of platelets to inflammatory responses. A recent paper in Science reports a pro-inflammatory role for platelets in inflammatory arthritis, showing that platelet-derived microparticles can promote immunopathology in the inflamed joint. - Innate immunity: A NOD to neutrophils
- Nature Reviews Immunology 10(3):157 (2010)
Four new studies show the ever-increasing complexity of vaccine approaches that are being developed to increase immunogenicity, improve safety and decrease production costs.Perhaps the 'simplest' approach to vaccination is to use the whole microorganism, which contains both the protective antigen or antigens and natural 'built-in' adjuvants. - B cells: Direct hit by IL-21
- Nature Reviews Immunology 10(3):158 (2010)
The relationship between a host and its intestinal microbiota may be even more complex and extensive than we previously anticipated, as suggested by a recent study in Nature Medicine. Clarke et al. - Tumour immunology: Antibodies lend support to tumours
- Nature Reviews Immunology 10(3):158 (2010)
It has been reported that interleukin-21 (IL-21) drives the differentiation of T follicular helper (TFH) cells and is essential for effective germinal centre B cell responses. However, it was not clear whether the B cells in the germinal centre are themselves dependent on IL-21 or if the key requirement for IL-21 is in promoting TFH cell functions. - Immune adaptations that maintain homeostasis with the intestinal microbiota
Hooper LV Macpherson AJ - Nature Reviews Immunology 10(3):159 (2010)
This study explains how B cells can contribute to cancer development. It shows that antibodies, by engaging activating Fc receptors for IgG (FcγRs) on myeloid cells in premalignant lesions, favour the generation of a chronic inflammatory environment that promotes carcinogenesis. - The regulation of IL-10 production by immune cells
Saraiva M O'Garra A - Nature Reviews Immunology 10(3):170 (2010)
Humans harbour nearly 100 trillion intestinal bacteria that are essential for health. Millions of years of co-evolution have moulded this human–microorganism interaction into a symbiotic relationship in which gut bacteria make essential contributions to human nutrient metabolism and in return occupy a nutrient-rich environment. Although intestinal microorganisms carry out essential functions for their hosts, they pose a constant threat of invasion owing to their sheer numbers and the large intestinal surface area. In this Review, we discuss the unique adaptations of the intestinal immune system that maintain homeostatic interactions with a diverse resident microbiota. - WASP: a key immunological multitasker
Thrasher AJ Burns SO - Nature Reviews Immunology 10(3):182 (2010)
Interleukin-10 (IL-10), a cytokine with anti-inflammatory properties, has a central role in infection by limiting the immune response to pathogens and thereby preventing damage to the host. Recently, an increasing interest in how IL10 expression is regulated in different immune cells has revealed some of the molecular mechanisms involved at the levels of signal transduction, epigenetics, transcription factor binding and gene activation. Understanding the specific molecular events that regulate the production of IL-10 will help to answer the remaining questions that are important for the design of new strategies of immune intervention. - Organization of immunological memory by bone marrow stroma
Tokoyoda K Hauser AE Nakayama T Radbruch A - Nature Reviews Immunology 10(3):193 (2010)
The Wiskott–Aldrich syndrome protein (WASP) is an important regulator of the actin cytoskeleton that is required for many haematopoietic and immune cell functions, including effective migration, phagocytosis and immune synapse formation. Loss of WASP activity leads to Wiskott–Aldrich syndrome, an X-linked disease that is associated with defects in a broad range of cellular processes, resulting in complex immunodeficiency, autoimmunity and microthrombocytopenia. Intriguingly, gain of function mutations cause a separate disease that is mainly characterized by neutropenia. Here, we describe recent insights into the cellular mechanisms of these two related, but distinct, human diseases and discuss their wider implications for haematopoiesis, immune function and autoimmunity. - Awakening dormant haematopoietic stem cells
Trumpp A Essers M Wilson A - Nature Reviews Immunology 10(3):201 (2010)
Immunological memory is a hallmark of the adaptive immune system. Plasma cells and memory B and T cells collectively provide protective immunity and effective secondary immune responses to invading pathogens. Here, we discuss how mesenchymal stromal cells regulate immunological memory by organizing defined numbers of dedicated survival niches for plasma cells and memory T cells in the bone marrow and also, to a lesser extent, in secondary lymphoid organs. An understanding of the biology of mesenchymal stromal cells and their interaction with cells of the immune system is key to fully understanding immunological memory. - NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production?
Tschopp J Schroder K - Nature Reviews Immunology 10(3):210 (2010)
Haematopoietic stem cells (HSCs) in mouse bone marrow are located in specialized niches as single cells. During homeostasis, signals from this environment keep some HSCs dormant, which preserves long-term self-renewal potential, while other HSCs actively self renew to maintain haematopoiesis. In response to haematopoietic stress, dormant HSCs become activated and rapidly replenish the haematopoietic system. Interestingly, three factors — granulocyte colony-stimulating factor, interferon-α and arsenic trioxide — have been shown to efficiently activate dormant stem cells and thereby could break their resistance to anti-proliferative chemotherapeutics. Thus, we propose that two-step strategies could target resistant leukaemic stem cells by priming tumours with activators of dormancy followed by chemotherapy or targeted therapies. - Erratum: Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function
- Nature Reviews Immunology 10(3):215 (2010)
The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that activates caspase 1, leading to the processing and secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. The NLRP3 inflammasome is activated by a wide range of danger signals that derive not only from microorganisms but also from metabolic dysregulation. It is unclear how these highly varied stress signals can be detected by a single inflammasome. In this Opinion article, we review the different signalling pathways that have been proposed to engage the NLRP3 inflammasome and suggest a model in which one of the crucial elements for NLRP3 activation is the generation of reactive oxygen species (ROS).
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