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Current Opinion in Immunology

Beate Heizmann, Philippe Kastner, Susan Chan
The IKZF family of transcription factors are essential regulators of lymphopoiesis. Ikaros, Helios, Aiolos and Eos function as transcriptional repressors and activators during T and B cell differentiation and in mature cell function, depending on the stage of development and/or cell type. Their potential mechanisms of action are varied. Ikaros family proteins partner with multiple complexes, including NuRD, PRC2 and transcription elongation factors, to modulate gene expression and the chromatin state. In humans, mutations in the IKZF genes are associated with B cell deficiency, leukemias and autoimmunity...
December 23, 2017: Current Opinion in Immunology
Shu Zhen Chong, Maximilien Evrard, Chi Ching Goh, Lai Guan Ng
Monocytes, dendritic cells (DCs) and macrophages have been classically categorized into the mononuclear phagocyte system (MPS) based on their similar functional and phenotypic characteristics. While an increasing amount of research has revealed substantial ontogenic and functional differences among these cells, the reasons behind their heterogeneity and strategic positioning in specific niches throughout the body are yet to be fully elucidated. In this review, we outline how recent advances in intravital imaging studies have dissected this phenomenon and have allowed us to appreciate how MPS cells exploit their regional niches to specialize and maximize their functional properties...
December 21, 2017: Current Opinion in Immunology
Trine A Kristiansen, Stijn Vanhee, Joan Yuan
The adult adaptive immune system is comprised of a wide spectrum of lymphocyte subsets with distinct antigen receptor repertoire profiles, effector functions, turnover times and anatomical locations, acting in concert to provide optimal host protection and self-regulation. While some lymphocyte populations are replenished by bone marrow hematopoietic stem cells (HSCs) through adulthood, others emerge during a limited window of time during fetal and postnatal life and sustain through self-replenishment. Despite fundamental implications in immune regeneration, early life immunity and leukemogenesis, the impact of developmental timing on lymphocyte output remains an under explored frontier in immunology...
December 19, 2017: Current Opinion in Immunology
Cody A Cunningham, Eric Y Helm, Pamela J Fink
Recent thymic emigrants (RTEs) are those peripheral T cells that have most recently completed thymic development and egress. Over the past decade, significant advances have been made in understanding the cell-extrinsic and cell-intrinsic requirements for RTE maturation to mature naïve (MN) T cells and in detailing the functional differences that characterize these two T cell populations. Much of this work has suggested that RTEs are hypo-functional versions of more mature T cells. However, recent evidence has indicated that rather than being defective T cells, RTEs are exquisitely adapted to their cellular niche...
December 16, 2017: Current Opinion in Immunology
J L McCarville, J S Ayres
Two distinct defense strategies provide a host with survival to infectious diseases: resistance and tolerance. Resistance is dependent on the ability of the host to kill pathogens. Tolerance promotes host health while having a neutral to positive impact of pathogen fitness. Immune responses are almost inevitably defined in terms of pathogen resistance. Recent evidence has shown, however, that several effects attributed to activation of innate and adaptive immune mechanisms, cannot be readily explained with the paradigm of immunity as effectors of microbial destruction...
December 15, 2017: Current Opinion in Immunology
Rekha Dhanwani, Mariko Takahashi, Sonia Sharma
In the cytoplasm, DNA is sensed as a universal danger signal by the innate immune system. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor/enzyme that catalyzes formation of 2'-5'-cGAMP, an atypical cyclic di-nucleotide second messenger that binds and activates the Stimulator of Interferon Genes (STING), resulting in recruitment of Tank Binding Kinase 1 (TBK1), activation of the transcription factor Interferon Regulatory Factor 3 (IRF3), and trans-activation of innate immune response genes, including type I Interferon cytokines (IFN-I)...
December 13, 2017: Current Opinion in Immunology
Johnny Bonnardel, Martin Guilliams
The combination between novel fate-mapping tools and single-cell RNA-sequencing technology has revealed the presence of multiple macrophage progenitors. This raises the fascinating possibility that what was once perceived as immense functional plasticity of macrophages could in fact come down to separate macrophage subsets performing distinct functions because of their differential cellular origin. The question of macrophage plasticity versus macrophage heterogeneity is broader than the difference between macrophages of embryonic or adult hematopoietic origin and is particularly relevant in the context of inflammation...
December 13, 2017: Current Opinion in Immunology
Bingyu Liu, Chengjiang Gao
RLRs (including RIG-I and MDA5) are the main receptors that recognize cytoplasmic viral RNA. Upon binding of viral RNA, RIG-I and MDA5 recruit mitochondria-localized MAVS to activate the downstream antiviral signaling. MAVS forms prion-like aggregates on the mitochondria after virus infection. The regulatory mechanisms for MAVS activation have been defined in various studies. Here, we summarize the recent advances about MAVS roles in antiviral immunity, discuss the regulation of MAVS activation, and suggest interesting areas for future research...
December 12, 2017: Current Opinion in Immunology
Veronika Horn, Antigoni Triantafyllopoulou
Whole genome duplications, an important step in cancer development, also occur in the macrophage lineage in disease: large multinucleated macrophages found within compact, ordered aggregates of immune cells, called granulomas, are a well-known histologic entity. Very recent work suggests that granuloma macrophages remarkably acquire epithelial cell features and the genotoxic stress response instructs granuloma macrophage genome duplications, suggesting that granuloma macrophages and pre-malignant epithelial cells may share common mechanisms of adaptation to chronic genotoxic stress...
December 1, 2017: Current Opinion in Immunology
Jesmond Dalli, Charles N Serhan
Understanding mechanisms that control immunity is central in the quest to gain insights into the etiopathology of many of the diseases that afflict modern societies. New results implicate the nervous system as a central player in controlling many aspects of both the innate and adaptive arms of the immune response. Furthermore it is now well appreciated that a novel group of autacoids termed as specialized proresolving mediators, which are enzymatically produced from essential fatty acids, orchestrate the immune response promoting the termination of inflammation as well as tissue repair and regeneration...
November 16, 2017: Current Opinion in Immunology
Eric Espinosa, Salvatore Valitutti
Mast cells are innate immune cells implicated in immune surveillance and defense. They are filled with secretory granules where a vast array of molecules endowed with multiple biological activities are stored. The process of granule secretion, named degranulation, is a tightly controlled biological phenomenon that allows mast cells to rapidly and efficiently release bioactive mediators in response to extracellular stimuli. MC degranulation allows fighting pathogens, limiting envenomation and contributes to tissue homeostasis...
November 13, 2017: Current Opinion in Immunology
David E Place, Thirumala-Devi Kanneganti
The inflammasome is a complex of proteins that through the activity of caspase-1 and the downstream substrates gasdermin D, IL-1β, and IL-18 execute an inflammatory form of cell death termed pyroptosis. Activation of this complex often involves the adaptor protein ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis. Here we discuss new regulatory mechanisms that have been identified for the canonical inflammasomes, the most recently identified NLRP9b inflammasome, and the new gasdermin family of proteins that mediate pyroptosis and other forms of regulated cell death...
November 9, 2017: Current Opinion in Immunology
Payel Sil, Ginger Muse, Jennifer Martinez
While classically considered a survival mechanism employed during nutrient scarcity, the autophagy pathway operates in multiple scenarios wherein a return to homeostasis or degradative removal of an invader is required. Now recognized as a pathway with vast immunoregulatory power, autophagy can no longer serve as a 'one size fits all' term, as its machinery can be recruited to different pathogens, at different times, with different outcomes. Both canonical autophagy and the molecularly related, yet divergent pathways non-canonical autophagy are key players in proper host defense and allow us an opportunity to tailor infectious disease intervention and treatment to its specific pathway...
November 7, 2017: Current Opinion in Immunology
Rui Martins, Sylvia Knapp
Heme is a vital, iron-containing prosthetic molecule present in a variety of proteins, of which hemoglobin is the most abundant. While the reactivity afforded by its central iron ion is essential for many cellular processes, it renders heme a potentially damaging molecule upon its release from hemeproteins, as it can catalyze the generation of reactive oxygen species. Severe intravascular hemolysis results in the leakage of vast amounts of hemoglobin, and subsequently, heme into the plasma. As such, heme is increasingly recognized as a major driving force for hemolysis-associated pathology including an increased risk for bacterial infections, due to its pro-oxidant, cytotoxic and immunomodulatory effects...
November 5, 2017: Current Opinion in Immunology
Patricia Costa-Reis, Kathleen E Sullivan
Monogenic lupus is rare, but its study has contributed immensely to a better understanding of the pathogenesis of systemic lupus erythematosus. The first forms identified were inherited complement deficiencies, which predisposed to lupus due to impaired tolerance, and aberrant clearance of apoptotic bodies and immune complexes. In recent years, several new monogenic disorders with a lupus-like phenotype have been described. These include forms that affect nucleic acid repair, degradation and sensing (TREX1, DNASE1L3), the type I interferon (IFN) pathway (SAMHD1, RNASEH2ABC, ADAR1, IFIH1, ISG15, ACP5, TMEM173) and B cell development checkpoints (PRKCD; RAG2)...
October 27, 2017: Current Opinion in Immunology
Lucy H Jackson-Jones, Cécile Bénézech
Natural IgM are crucial for early protection against infection and play an important homeostatic function by clearing dead cells. The production of IgM is ensured by a population of B cells with innate-like properties: their response is rapidly activated by innate signals early during the onset of infection. The main reservoir of innate-like B cells (IBCs) are the serous cavities, but their maintenance and activation depends on their relocation to a variety of lymphoid tissues. Recent advances indicate that fat-associated lymphoid clusters (FALCs) and milky spots contribute to local IgM secretion and play a central role in the localisation and regulation of IBC function...
October 24, 2017: Current Opinion in Immunology
Bernice Lo, Michael J Lenardo
No abstract text is available yet for this article.
December 2017: Current Opinion in Immunology
Stefanie Kretschmer, Min Ae Lee-Kirsch
The monogenic type I interferonopathies comprise a heterogenous group of disorders of the innate immune system associated with constitutive activation of antiviral type I interferon (IFN). Despite a remarkable phenotypic diversity, type I interferonopathies are commonly characterized by autoinflammation and varying degrees of autoimmunity or immunodeficiency. The elucidation of the underlying genetic causes has revealed novel cell-intrinsic mechanisms that protect the organism against inappropriate immune recognition of self nucleic acids by cytosolic sensors such as cGAS or MDA5 through metabolizing or processing of intracellular DNA or RNA...
December 2017: Current Opinion in Immunology
Noel R Rose
Infections often precede the onset of autoimmune disease and molecular (or epitope) mimicry is a plausible link. Cross-reacting epitopes are common between an infecting microorganism and the host because negative selection of self-reactive T-cells and B-cells is frequently incomplete. Complete eradication could lead to major voids in the immunologic repertoire. The association of an autoimmune disease with a microbial epitope may signify a causal relationship with the organism, an indirect connection through bystander effects, persistent infection or coincidence...
December 2017: Current Opinion in Immunology
Frédéric Rieux-Laucat
The autoimmune lymphoproliferative syndrome (ALPS) is a non-malignant and non-infectious uncontrolled proliferation of lymphocytes accompanied by autoimmune cytopenia. This clinical entity was recognized in the mid 60s and its genetic etiology was described in 1995 by the discovery of the FAS gene mutations. This was the first description of a monogenic cause of autoimmunity but its non-Mendelian expression remained elusive until the description of somatic and germline mutations in ALPS patients. The related apoptosis defect accounts for the accumulation of autoreactive lymphocytes as well as for specific clinical and biological features that distinguish the ALPS-FAS from other monogenic causes of ALPS such as somatic mutations of RAS or the recently described CTLA-4 insufficiency...
December 2017: Current Opinion in Immunology
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