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Current Opinion in Immunology

Steven D Scoville, Aharon G Freud, Michael A Caligiuri
Innate lymphoid cells (ILCs) are critical to effective immune surveillance against pathogens, have malignant counterparts, and contribute to disease. Thus, it is important to understand ILC development. All ILCs are derived from the common lymphoid progenitor cell; however, the exact mechanisms and signals that initiate their divergence from T cells, B cells and one and other are incompletely understood. Evidence now supports a stepwise developmental process that includes distinct cellular intermediates, progressively narrowed differentiation, and some plasticity...
December 19, 2018: Current Opinion in Immunology
Christoph Sn Klose, David Artis
The cardinal signs of inflammation suggest a close connection between the nervous system and the immune system. However, the cellular and molecular basis of these interactions remains incompletely defined. Recent research has demonstrated that tissue-resident innate lymphoid cells (ILCs) obtain neuronal signals, particularly at mucosal barriers, where ILCs regulate tissue homeostasis. New developments in our understanding of neuronal regulation of ILCs provide insight into how immune responses in tissues are precisely targeted, spatially regulated, and how ILCs sense environmental changes and disturbance of tissue homeostasis...
December 7, 2018: Current Opinion in Immunology
Alexander David Barrow, Marco Colonna
Innate lymphoid cells (ILCs) constitute a heterogeneous population of cytokine-secreting cells that colonize different tissues and are heavily reliant on cytokines and other secreted factors for their development, maintenance and effector functions. Most ILCs are tissue resident and differentiate in non-lymphoid peripheral tissues. As tissue-resident sentinels, ILCs must rapidly identify pathogens or malignancy in an effort to return the tissue to homeostasis. Here we review the mechanisms that ILCs employ to sense cytokines and other potent immunoregulatory factors that promote their development in different tissues as well as the ability to distinguish pathogenic versus healthy tissue microenvironments and highlight the importance of these pathways for human disease...
December 4, 2018: Current Opinion in Immunology
Ronald N Germain, Yuefeng Huang
A cardinal feature of the T-cell adaptive immune system is the antigen-dependent activation of naïve T cells in secondary lymphoid sites, followed by the migration of the resultant effector cells through the efferent lymph to the blood and then into a peripheral tissue site of infection or tumor growth. In contrast, the current view of innate lymphocytes (ILCs), the innate counterparts of T cells, is that they are tissue-resident cells, adapted to their specific environments during development and performing their effector functions locally upon cytokine stimulation...
November 22, 2018: Current Opinion in Immunology
Evangelos Andreakos, Ivan Zanoni, Ioanna E Galani
Lambda interferons (IFNλs, type III IFNs or interleukins-28/29) were described fifteen years ago as novel cytokines sharing structural and functional homology with IL-10 and type I IFNs, respectively. IFNλs engage a unique receptor complex comprising IFNLR1 and IL10R2, nevertheless they share signaling cascade and many functions with type I IFNs, questioning their possible non-redundant roles and overall biological importance. Here, we review the latest evidence establishing the primacy of IFNλs in front line protection at anatomical barriers, mediating antiviral immunity before type I IFNs...
November 3, 2018: Current Opinion in Immunology
Malika Hale, David J Rawlings, Shaun W Jackson
High titers of pathogenic autoantibodies are a hallmark of many autoimmune diseases. However, much remains unknown about the self-reactive plasma cells that are key mediators of disease. We propose a model in which the varying efficacy of precursor B cell depletion for the treatment of humoral autoimmunity can be explained by differences in the relative contributions of pathogenic antibodies by short-lived versus long-lived plasma cells. Beyond therapeutic considerations, this model suggests that we can infer the cellular source of disease-associated autoantibodies by the durability of serum titers following B cell depletion...
October 31, 2018: Current Opinion in Immunology
Matteo Ugolini, Leif E Sander
Immune detection of microbial viability is increasingly recognized as a potent driver of innate and adaptive immune responses. Here we describe recent mechanistic insights into the process of how the immune system discriminates between viable and non-viable microbial matter. Accumulating evidence suggests a key role for microbial RNA as a widely conserved viability associated PAMP (vita-PAMP) and a molecular signal of increased infectious threat. Toll-like receptor 8 (TLR8) has recently emerged as a critical sensor for viable bacteria, ssRNA viruses, and archaea in human antigen presenting cells (APC)...
October 23, 2018: Current Opinion in Immunology
Daniel B Stetson
No abstract text is available yet for this article.
December 2018: Current Opinion in Immunology
Narcisa Martinez-Quiles, Raphaela Goldbach-Mansky
Autoinflammatory diseases are hyperinflammatory, immune dysregulatory diseases caused by innate immune cells dysregulation that present typically in the perinatal period with systemic and organ-targeted inflammation, but with improved genetic testing and the development of diagnostic criteria, milder and later-onset forms are being detected in adulthood. While the discovery of gain-of-function mutations in innate sensors linked to the production of proinflammatory cytokines provided the bases for anti-cytokine therapies that changed disease and patient outcomes, the field is expanding with the increasing discovery of disease-causing loss-of-function mutations in genes with cellular house-keeping functions that affect cell homeostasis and when dysregulated trigger innate inflammatory pathways...
December 2018: Current Opinion in Immunology
Giovanni Ristori, Denise Faustman, Giuseppe Matarese, Silvia Romano, Marco Salvetti
At the end of past century, when the prevailing view was that treatment of autoimmunity required immune suppression, experimental evidence suggested an approach of immune-stimulation such as with the BCG vaccine in type 1 diabetes (T1D) and multiple sclerosis (MS). Translating these basic studies into clinical trials, we showed the following: BCG harnessed the immune system to 'permanently' lower blood sugar, even in advanced T1D; BCG appeared to delay the disease progression in early MS; the effects were long-lasting (years after vaccination) in both diseases...
December 2018: Current Opinion in Immunology
Swati Phalke, Philippa Marrack
B cells affect human and animal health in numerous ways. They are the precursors for the antibody-secreting plasma cells and they also take up antigen, particularly antigen for which they bear-specific receptors, very efficiently and thus present antigen to T cells. The T cell-B cell interactions that thus occur serve not only to affect the B cell, but also, the T cell partner of the interaction. B cells are known to be quite heterogeneous. The different subpopulations of B cells contribute to different types of immune responses...
December 2018: Current Opinion in Immunology
Mark Noviski, Julie Zikherman
A substantial fraction of mature naïve B cells recognize endogenous antigens, and this autoreactivity must be controlled to prevent autoantibody secretion. Selective downregulation of the IgM BCR on autoreactive B cells has long been appreciated, and recent findings illustrate how this might impose tolerance. The BCR isotype maintained on autoreactive B cells, IgD, is less sensitive to endogenous antigens than IgM. This reduced sensitivity may be conferred by structural properties of IgD and/or differential association with activating and inhibitory co-receptors...
December 2018: Current Opinion in Immunology
Simon Fillatreau
B cells can generate several types of antibody-secreting cells, including plasmablasts that divide and are short lived, as well as plasma cells that do not proliferate and can persist for extended time periods. Here, we discuss the identification of a novel subset of non-dividing plasma cells specialized in the production of interleukin(IL)-10. These cells develop at steady state, including in germ-free mice, via a mechanism dependent on the B cell receptor for antigen and possibly involving the recognition of damaged cells...
December 2018: Current Opinion in Immunology
Mohamed Oukka, Estelle Bettelli
CD4+ T helper (Th) cells play a central role in orchestrating protective immunity but also in autoimmunity. Multiple Sclerosis (MS) is a human autoimmune disease of the central nervous system (CNS) characterized by the infiltration of inflammatory lymphocytes and myeloid cells into the brain and spinal cord, leading to demyelination, axonal damage, and progressive loss of motor functions. The release of T cells in the circulation and their migration in the central nervous system are key and tightly regulated processes which have been targeted to decrease CD4+ T cell presence in the CNS and limit disease progression...
December 2018: Current Opinion in Immunology
Britta E Jones, Megan D Maerz, Jane H Buckner
IL-6 is implicated in the development and progression of autoimmune diseases in part by influencing CD4 T cell lineage and regulation. Elevated IL-6 levels drive inflammation in a wide range of autoimmune diseases, some of which are also characterized by enhanced T cell responses to IL-6. Notably, the impact of IL-6 on inflammation is contextual in nature and dependent on the cell type, cytokine milieu and tissue. Targeting the IL-6/IL-6R axis in humans has been shown to successfully ameliorate a subset of autoimmune conditions...
December 2018: Current Opinion in Immunology
Naomi I Maria, Anne Davidson
Recent advances in the field of autoimmunity have identified numerous dysfunctional pathways in Systemic Lupus Erythematosus (SLE), including aberrant clearance of nucleic-acid-containing debris and immune complexes, excessive innate immune activation leading to overactive type I IFN signalling, and abnormal B and T cell activation. On the background of genetic polymorphisms that reset thresholds for immune responses, multiple immune cells contribute to inflammatory amplification circuits. Neutrophils activated by immune complexes are a rich source of immunogenic nucleic acids...
December 2018: Current Opinion in Immunology
Xianfang Wu, Andrew C Kwong, Charles M Rice
Stem cells are important for growth and regeneration given their ability to self-renew and differentiate into mature cells. Resistance to certain viral infections has been established as a phenotype of stem cells, a protection in line with their important physiological function. Antiviral resistance is critical to all cells, but it is differentially regulated between stem cells and differentiated cells. Stem cells utilize antiviral RNA interference, interferon-independent repression of endogenous retroviruses and intrinsic expression of antiviral interferon-stimulated genes...
October 20, 2018: Current Opinion in Immunology
Elise Dalmas
Increasing evidence suggests a role for the immune system to finely tune metabolic homeostasis. The possibility that the immune system can likewise regulate islet endocrine function has only commenced drawing attention. Islet beta cells are the main producers of insulin and have to dynamically respond to fluctuating insulin demands of the body. While inflammation has long been considered as an important pathogenic feature of diabetes development, pioneer studies have shown that immune cells reside inside pancreatic islets under steady state and that components of the immune system can promote beta cell insulin production...
October 17, 2018: Current Opinion in Immunology
Pietro Scaturro, Andreas Pichlmair
One of the best-studied cellular responses to toxic signals and pathogens is programmed cell death. Over the past years, it became apparent that the specific mechanisms of cell death have tremendous influence at both cellular and organismal level, highlighting the importance of sensors and pathways involved in this decision-making process. Central signalling molecules involved in a variety of cell death pathways are reactive oxygen species (ROS). However, the molecular mechanisms regulating differential responses and cellular fates to distinct ROS levels remain incompletely understood...
October 17, 2018: Current Opinion in Immunology
Jared M Andrews, Jacqueline E Payton
Normal B cell development, activation, and terminal differentiation depend on the intricate dynamics of cooperating epigenetic and non-coding components to control the level and timing of expression of thousands of genes. Recent genome-wide studies have integratively mapped changes in the chromatin landscape, DNA methylome, 3-dimensional interactome, and coding and non-coding transcriptomes of normal and malignant B cells. Genetic ablation in human cells and mouse models has begun to elucidate the coordinated roles of essential epigenetic modifiers, key transcription factors, and long non-coding RNAs in B cell biology...
October 17, 2018: Current Opinion in Immunology
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