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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
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...
October 30, 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
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
Takeshi Egawa, Deepta Bhattacharya
B cell activation and differentiation are associated with marked changes in proliferative and effector functions. Each stage of B cell differentiation thus has unique metabolic demands. New studies have provided insight on how nutrient uptake and usage by B cells are regulated by B cell receptor signals, autophagy, mammalian target of rapamycin, and transcriptional control of transporters and rate-limiting enzymes. A recurring theme is that these pathways play distinct roles ranging from survival to antibody production, depending on the B cell fate...
October 16, 2018: Current Opinion in Immunology
Munir Akkaya, Susan K Pierce
Throughout their lifetimes B cells shift metabolic gears to move rapidly from quiescent states to full out proliferative expansion and back again. Here we discuss recent findings that shed light on how B cells rapidly shift gears to metabolically fuel expansion and then just as rapidly down shift during phases of receptor rearrangements to ensure genome stability. We also discuss the link between metabolic activity and fate decisions in B cells.
October 9, 2018: Current Opinion in Immunology
Selene Glück, Andrea Ablasser
Senescence is a multistep cellular program featuring a stable cell cycle arrest, which occurs upon exposure to various stressors. Senescent cells exhibit metabolic activity and hypertrophy and produce a multitude of factors with both cell intrinsic as well as non-cell autonomous functions. These factors are collectively referred to as the senescence-associated secretory phenotype (SASP). Recently, the DNA sensor cyclic GMP AMP synthase (cGAS) and the adaptor stimulator of interferon genes (STING) have been reported to be critically involved in the regulation of senescence...
October 5, 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...
October 4, 2018: Current Opinion in Immunology
Flavie Coquel, Christoph Neumayer, Yea-Lih Lin, Philippe Pasero
Cytosolic DNA of endogenous or exogenous origin is sensed by the cGAS-STING pathway to activate innate immune responses. Besides microbial DNA, this pathway detects self-DNA in the cytoplasm of damaged or abnormal cells and plays a central role in antitumor immunity. The mechanism by which cytosolic DNA accumulates under genotoxic stress conditions is currently unclear, but recent studies on factors mutated in the Aicardi-Goutières syndrome cells, such as SAMHD1, RNase H2 and TREX1, are shedding new light on this key process...
October 4, 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...
October 3, 2018: Current Opinion in Immunology
Johan Garaude
The reprogramming of cellular metabolism has emerged as a major aspect of innate immune cell activation. Mitochondria, which are well known for their critical functions in cellular bioenergetics and metabolism, also serve innate immune purposes by providing specific signaling platforms. Latest advances in our understanding of innate immune receptor-mediated metabolic reprogramming have unraveled specific immune functions of mitochondrial metabolites that place mitochondrial metabolism and particularly the mitochondrial respiratory chain at the center of innate immunity...
October 1, 2018: Current Opinion in Immunology
Jennifer Martinez
LC3-associated phagocytosis (LAP) exists at the crossroads of the two evolutionary pathways of phagocytosis and autophagy. When a phagocyte engulfs an extracellular particle that engages receptor signaling, components of the autophagy machinery and Rubicon are recruited to the cargo-containing phagosome or LAPosome. Formation of the LAPosome is critical for both cargo clearance as well as mediating the proper signaling cascade. Globally, LAP functions as an immunosuppressive mechanism, as LAP deficiency often results in hyperinflammation...
October 1, 2018: Current Opinion in Immunology
Silvina Del Carmen, Sophie M Hapak, Sourav Ghosh, Carla V Rothlin
Coagulopathies and inflammatory diseases, ostensibly, have distinct underlying molecular bases. Notwithstanding, both are host defense mechanisms to physical injury. In invertebrates, clotting can function directly in anti-pathogen defense. Molecules of the vertebrate clotting cascade have also been directly linked to the regulation of inflammation. We posit that thrombophilia may provide resistance against pathogens in vertebrates. The selective pressure of improved anti-pathogen defense may have retained mutations associated with a thrombophilic state in the human population and directly contributed to enhanced inflammation...
September 27, 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...
September 27, 2018: Current Opinion in Immunology
Chetna Soni, Boris Reizis
High-affinity antibodies to double-stranded DNA are a hallmark of systemic lupus erythematosus (SLE) and are thought to contribute to disease flares and tissue inflammation such as nephritis. Notwithstanding their clinical importance, major questions remain about the development and regulation of these pathogenic anti-DNA responses. These include the mechanisms that prevent anti-DNA responses in healthy subjects, despite the constant generation of self-DNA and the abundance of DNA-reactive B cells; the nature and physical form of antigenic DNA in SLE; the regulation of DNA availability as an antigen; and potential therapeutic strategies targeting the pathogenic DNA in SLE...
September 24, 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...
September 21, 2018: Current Opinion in Immunology
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