Ion homeostasis and ion channels in NLRP3 inflammasome activation and regulation.
e;n P Abstract The NLRP3 inflammasome is a multiprotein platform for the activation of caspase-1, which in turn drives inflammation through the activation of proinflammatory cytokines, such as IL-1β. In contrast to the majority of pattern recognition receptors, NLRP3 inflammasome can be triggered by a plethora of pathogen-derived or endogenous activators, which perturb intracellular ion homeostasis. Here, we discuss how the complex interplay of ion fluxes contributes to canonical, non-canonical, and alternative NLRP3 activation pathways that induce IL-1β secretion from immune cells. Particular attention ...
Source: Current Opinion in Immunology - March 16, 2018 Category: Allergy & Immunology Authors: Hafner-Bratkovič I, Pelegrín P Tags: Curr Opin Immunol Source Type: research

Driving CARs on the uneven road of antigen heterogeneity in solid tumors.
Abstract Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor res...
Source: Current Opinion in Immunology - March 16, 2018 Category: Allergy & Immunology Authors: Chen N, Li X, Chintala NK, Tano ZE, Adusumilli PS Tags: Curr Opin Immunol Source Type: research

Cancer vaccines: translation from mice to human clinical trials.
Abstract Therapeutic cancer vaccines have been a long-sought approach to harness the exquisite specificity of the immune system to treat cancer, but until recently have not had much success as single agents in clinical trials. However, new understanding of the immunoregulatory mechanisms exploited by cancers has allowed the development of approaches to potentiate the effect of vaccines by removing the brakes while the vaccines step on the accelerator. Thus, vaccines that had induced a strong T cell response but no clinical therapeutic effect may now reach their full potential. Here, we review a number of promising...
Source: Current Opinion in Immunology - March 16, 2018 Category: Allergy & Immunology Authors: Maeng H, Terabe M, Berzofsky JA Tags: Curr Opin Immunol Source Type: research

Immune-based identification of cancer patients at high risk of progression.
man C Abstract Tumors are highly heterogeneous structures where malignant cells interact with a large variety of cell populations, including a clinically-relevant immune component. We review and compare the most recent methods designed to analyze and quantify the composition of immune and stromal microenvironment of tumors and discuss their use in identification of patients for high risk of progression. If the impact of the various immune components on patient's relapse share common rules in most malignancies, clear cell renal cell tumors behave differently with regards to immunity. We focus on this specific patho...
Source: Current Opinion in Immunology - March 16, 2018 Category: Allergy & Immunology Authors: Vano YA, Petitprez F, Giraldo NA, Fridman WH, Sautès-Fridman C Tags: Curr Opin Immunol Source Type: research

Oncolytic viruses and immunity.
Abstract Initially, direct oncolysis was thought to be the sole mechanism through which oncolytic viruses (OVs) exert their anti-tumor effect, and the immune system was perceived as the major obstacle in oncolytic virotherapy. Over the last decade, there has been a lot of debate on whether the immune system is a friend or foe of OVs. However, we are now at a stage where the initial thinking has been reversed as a result of compelling evidence that the immune system plays a critical role in the success of oncolytic virotherapy. In this review we discuss the importance of the involvement of innate and adaptive immun...
Source: Current Opinion in Immunology - March 15, 2018 Category: Allergy & Immunology Authors: Chaurasiya S, Chen NG, Fong Y Tags: Curr Opin Immunol Source Type: research

Immune signatures predicting responses to immunomodulatory antibody therapy.
This article reviews seminal papers mostly from the past two years of progress in this area of intense investigation, and mostly in melanoma, the tumour type for which the largest body of data exists thus far. PMID: 29550661 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - March 15, 2018 Category: Allergy & Immunology Authors: Pawelec G Tags: Curr Opin Immunol Source Type: research

Plasticity of myeloid-derived suppressor cells in cancer.
Abstract In recent years, myeloid-derived suppressor cells (MDSC) have emerged as one of the major inhibitors of immune effector cell function in cancer. MDSC represent a heterogeneous population of largely immature myeloid cells that are characterized by a pathological state of activation and display potent immune suppressive activity. Two major subsets of MDSC have been identified: monocytic (M-MDSC) and polymorphonuclear (PMN-MDSC). PMN-MSDC share phenotypic and morphologic features with neutrophils, whereas M-MDSC are similar to monocytes and are characterized by high plasticity. Differentiation of M-MDSC to m...
Source: Current Opinion in Immunology - March 13, 2018 Category: Allergy & Immunology Authors: Tcyganov E, Mastio J, Chen E, Gabrilovich DI Tags: Curr Opin Immunol Source Type: research

Myeloid derived-suppressor cells: their role in cancer and obesity.
This article reviews the data supporting this hypothesis, the role of leptin and fatty acid metabolism in the induction of MDSC, and the surprising finding that although MDSC promote tumor progression, they are protective against some of the metabolic dysfunction associated with obesity. PMID: 29544121 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - March 12, 2018 Category: Allergy & Immunology Authors: Ostrand-Rosenberg S Tags: Curr Opin Immunol Source Type: research

NKG2D and its ligands in cancer.
Abstract NKG2D is an activating immune receptor expressed by NK and effector T cells. Induced expression of NKG2D ligand on tumor cell surface during oncogenic insults renders cancer cells susceptible to immune destruction. In advanced human cancers, tumor cells shed NKG2D ligand to produce an immune soluble form as a means of immune evasion. Soluble NKG2D ligands have been associated with poor clinical prognosis in cancer patients. Harnessing NKG2D pathway is considered a viable avenue in cancer immunotherapy over recent years. In this review, we will discuss the progress and perspectives. PMID: 29525346 [Pu...
Source: Current Opinion in Immunology - March 8, 2018 Category: Allergy & Immunology Authors: Dhar P, Wu JD Tags: Curr Opin Immunol Source Type: research

Metabolites, genome organization, and cellular differentiation gene programs.
Abstract The nutrient environment and metabolism play a dynamic role in cellular differentiation and research is elucidating the mechanisms that contribute to this process. Metabolites serve as an effective bridge that helps to translate information about nutrient states into specific interpretations of the genome. Part of this activity relates to the role for metabolites in regulating epigenetic processes as well as a newly appreciated role for metabolites in the regulation of genome organization. In this review, we will highlight recent research that has defined roles for metabolism in the organization and inter...
Source: Current Opinion in Immunology - March 8, 2018 Category: Allergy & Immunology Authors: Chisolm DA, Weinmann AS Tags: Curr Opin Immunol Source Type: research

P2X receptor-ion channels in the inflammatory response in adipose tissue and pancreas-potential triggers in onset of type 2 diabetes?
Abstract Type 2 diabetes is reaching an alarming prevalence worldwide. Its complex pathogenesis certainly includes a pivotal role of low-grade inflammation, which could be triggered by excessive purinergic signaling. In this complex scenario, extracellular ATP impairs the function of two key players: β-cell and adipose tissue. In the former, P2Y and possibly some P2X receptors-ion channels regulate insulin secretion, but it is still debated whether excessive ATP can via P2X receptors impair β-cell function directly or whether cell damage is due to an excessive systemic release of cytokines. In human adip...
Source: Current Opinion in Immunology - March 6, 2018 Category: Allergy & Immunology Authors: Novak I, Solini A Tags: Curr Opin Immunol Source Type: research

Humoral immune responses to infection: common mechanisms and unique strategies to combat pathogen immune evasion tactics.
Abstract Humoral immune responses are crucial for protection against invading pathogens and are the underlying mechanism of protection for most successful vaccines. Our understanding of how humoral immunity develops is largely based on animal models utilizing experimental immunization systems. While these studies have made enormous progress for the field and have defined many of the fundamental principles of B cell differentiation and function, we are only now beginning to appreciate the complexities of humoral immune responses induced by infection. Co-evolution of the adaptive immune system and the pathogenic wor...
Source: Current Opinion in Immunology - February 22, 2018 Category: Allergy & Immunology Authors: Sebina I, Pepper M Tags: Curr Opin Immunol Source Type: research

Editorial overview: Innate immunity: The finely tuned STING of innate immunity.
PMID: 29475574 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - February 20, 2018 Category: Allergy & Immunology Authors: Randolph GJ Tags: Curr Opin Immunol Source Type: research

Transcriptional and epigenetic regulation of innate-like T lymphocyte development.
Abstract Invariant Natural Killer T (iNKT) cells are a heterogeneous innate T cell population that recognizes lipid antigens. Despite the monospecific nature of their T cell receptor, iNKT cells differentiate into stable sublineages during thymic development, before foreign antigen encounter. How iNKT cell subsets acquire and maintain their functional programs is a central question in innate lymphocyte biology. Global transcriptional and epigenetic profiling of iNKT subsets has provided insights into the internal wiring of these subsets that defines their identity. Comparison of the iNKT transcriptional programs w...
Source: Current Opinion in Immunology - February 13, 2018 Category: Allergy & Immunology Authors: Verykokakis M, Kee BL Tags: Curr Opin Immunol Source Type: research

Chemical sensing in development and function of intestinal lymphocytes.
Abstract The immune system of the intestinal tract has the challenging task of recognizing and eliminating intestinal pathogens while maintaining tolerance to dietary and commensal antigens; therefore, it must be able to sense environmental cues within the intestine and mount suitable responses dictated by their pathogenic or nonpathogenic nature. The aryl hydrocarbon receptor (AHR) was originally characterized as a chemical sensor of the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) [12]. More recently, AHR has emerged as a major chemical sensor expressed in many intestinal immune cells that ...
Source: Current Opinion in Immunology - February 13, 2018 Category: Allergy & Immunology Authors: Cervantes-Barragan L, Colonna M Tags: Curr Opin Immunol Source Type: research

Control of B-1a cell development by instructive BCR signaling.
Abstract B-1a cells remain one of the most enigmatic lymphocyte subsets. In this review, we discuss recent advances in our understanding of the development of these cells and their regulation by the transcription factors Bhlhe41 and Arid3a as well as by the RNA-binding protein Lin28b. A large body of literature supports an instructive role of BCR signaling in B-1a cell development and lineage commitment, which is initiated only after signaling from an autoreactive BCR. While both fetal and adult hematopoiesis can generate B-1a cells, the contribution of adult hematopoiesis to the B-1a cell compartment is low under...
Source: Current Opinion in Immunology - February 3, 2018 Category: Allergy & Immunology Authors: Kreslavsky T, Wong JB, Fischer M, Skok JA, Busslinger M Tags: Curr Opin Immunol Source Type: research

The regulation of lymphocyte activation and proliferation.
Abstract Activation induced proliferation and clonal expansion of antigen specific lymphocytes is a hallmark of the adaptive immune response to pathogens. Recent studies identify two distinct control phases. In the first T and B lymphocytes integrate antigen and additional costimuli to motivate a programmed proliferative burst that ceases with a return to cell quiescence and eventual death. This proliferative burst is autonomously timed, ensuring an appropriate response magnitude whilst preventing uncontrolled expansion. This initial response is subject to further modification and extension by a range of signals t...
Source: Current Opinion in Immunology - February 2, 2018 Category: Allergy & Immunology Authors: Heinzel S, Marchingo JM, Horton MB, Hodgkin PD Tags: Curr Opin Immunol Source Type: research

Natural killer cell education in human health and disease.
Abstract Natural killer (NK) cells maintain immune homeostasis by detecting and eliminating damaged cells. Simultaneous activating and inhibitory input are integrated by NK cells, with the net signal prompting cytotoxicity and cytokine production, or inhibition. Chief among the inhibitory ligands for NK cells are 'self' human leukocyte antigen (HLA) molecules, which are sensed by killer immunoglobulin-like receptors (KIR). Through a process called 'education', the functional capabilities of each NK cell are counterbalanced by their sensitivity for inhibition by co-inherited 'self' HLA. HLA and their ligands, the k...
Source: Current Opinion in Immunology - January 27, 2018 Category: Allergy & Immunology Authors: Boudreau JE, Hsu KC Tags: Curr Opin Immunol Source Type: research

The Ikaros family in lymphocyte development.
Abstract 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....
Source: Current Opinion in Immunology - December 23, 2017 Category: Allergy & Immunology Authors: Heizmann B, Kastner P, Chan S Tags: Curr Opin Immunol Source Type: research

Illuminating the covert mission of mononuclear phagocytes in their regional niches.
Abstract 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...
Source: Current Opinion in Immunology - December 21, 2017 Category: Allergy & Immunology Authors: Chong SZ, Evrard M, Goh CC, Ng LG Tags: Curr Opin Immunol Source Type: research

The influence of developmental timing on B cell diversity.
Abstract 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 imp...
Source: Current Opinion in Immunology - December 19, 2017 Category: Allergy & Immunology Authors: Kristiansen TA, Vanhee S, Yuan J Tags: Curr Opin Immunol Source Type: research

Reinterpreting recent thymic emigrant function: defective or adaptive?
Abstract 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 ce...
Source: Current Opinion in Immunology - December 16, 2017 Category: Allergy & Immunology Authors: Cunningham CA, Helm EY, Fink PJ Tags: Curr Opin Immunol Source Type: research

Disease tolerance: concept and mechanisms.
Abstract 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. This review focuses on integrating t...
Source: Current Opinion in Immunology - December 15, 2017 Category: Allergy & Immunology Authors: McCarville JL, Ayres JS Tags: Curr Opin Immunol Source Type: research

Developmental control of macrophage function.
Abstract 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...
Source: Current Opinion in Immunology - December 13, 2017 Category: Allergy & Immunology Authors: Bonnardel J, Guilliams M Tags: Curr Opin Immunol Source Type: research

Cytosolic sensing of immuno-stimulatory DNA, the enemy within.
Abstract 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). Activation of the pro-inflammatory cGAS-STING-IRF3 response i...
Source: Current Opinion in Immunology - December 13, 2017 Category: Allergy & Immunology Authors: Dhanwani R, Takahashi M, Sharma S Tags: Curr Opin Immunol Source Type: research

Regulation of MAVS activation through post-translational modifications.
Abstract 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. PMID: 29245018 [PubMed - as supplied by publisher] (Sou...
Source: Current Opinion in Immunology - December 12, 2017 Category: Allergy & Immunology Authors: Liu B, Gao C Tags: Curr Opin Immunol Source Type: research

DNA damage signaling and polyploid macrophages in chronic inflammation.
Abstract 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. Exploring these mechan...
Source: Current Opinion in Immunology - December 1, 2017 Category: Allergy & Immunology Authors: Horn V, Triantafyllopoulou A Tags: Curr Opin Immunol Source Type: research

Editorial overview: Autoimmunity: New genomics approaches are improving our understanding of autoimmunity.
PMID: 29173328 [PubMed - in process] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - November 29, 2017 Category: Allergy & Immunology Authors: Lo B, Lenardo MJ Tags: Curr Opin Immunol Source Type: research

Immunoresolvents signaling molecules at intersection between the brain and immune system.
Abstract 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. T...
Source: Current Opinion in Immunology - November 16, 2017 Category: Allergy & Immunology Authors: Dalli J, Serhan CN Tags: Curr Opin Immunol Source Type: research

New roles and controls of mast cells.
Abstract 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. However, it is also a potentially harmful response that plays a key role in the ...
Source: Current Opinion in Immunology - November 13, 2017 Category: Allergy & Immunology Authors: Espinosa E, Valitutti S Tags: Curr Opin Immunol Source Type: research

Type I interferon-mediated autoinflammation and autoimmunity.
Abstract 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 p...
Source: Current Opinion in Immunology - November 9, 2017 Category: Allergy & Immunology Authors: Kretschmer S, Lee-Kirsch MA Tags: Curr Opin Immunol Source Type: research

Recent advances in inflammasome biology.
Abstract 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 gasd...
Source: Current Opinion in Immunology - November 9, 2017 Category: Allergy & Immunology Authors: Place DE, Kanneganti TD Tags: Curr Opin Immunol Source Type: research

A ravenous defense: canonical and non-canonical autophagy in immunity.
Abstract 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 opportunit...
Source: Current Opinion in Immunology - November 7, 2017 Category: Allergy & Immunology Authors: Sil P, Muse G, Martinez J Tags: Curr Opin Immunol Source Type: research

Negative selection, epitope mimicry and autoimmunity.
Abstract 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. There are well-established examples of a m...
Source: Current Opinion in Immunology - November 2, 2017 Category: Allergy & Immunology Authors: Rose NR Tags: Curr Opin Immunol Source Type: research

Monogenic lupus: it's all new!
Abstract 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, TMEM...
Source: Current Opinion in Immunology - October 27, 2017 Category: Allergy & Immunology Authors: Costa-Reis P, Sullivan KE Tags: Curr Opin Immunol Source Type: research

Control of innate-like B cell location for compartmentalised IgM production.
cute;zech C Abstract 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 secret...
Source: Current Opinion in Immunology - October 24, 2017 Category: Allergy & Immunology Authors: Jackson-Jones LH, Bénézech C Tags: Curr Opin Immunol Source Type: research

What's up in the ALPS.
Abstract 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...
Source: Current Opinion in Immunology - October 23, 2017 Category: Allergy & Immunology Authors: Rieux-Laucat F Tags: Curr Opin Immunol Source Type: research

Molecular control of regulatory T cell development and function.
Abstract Treg cells expressing the transcription factor Foxp3 are essential for immunological tolerance and homeostasis. Recent genome-wide studies have revealed that Foxp3(+) natural Treg cells possess a number of unique transcriptional and epigenetic features, which appear to be acquired along the course of Treg cell development and maintained throughout their lifespan. These studies also provide novel insights into how genomic variations contribute to genetic susceptibility to human autoimmune diseases by affecting Treg cell development and function. PMID: 29065384 [PubMed - as supplied by publisher] (Sour...
Source: Current Opinion in Immunology - October 21, 2017 Category: Allergy & Immunology Authors: Kitagawa Y, Sakaguchi S Tags: Curr Opin Immunol Source Type: research

Insights into immune tolerance from AIRE deficiency.
Abstract AIRE is a well-established master regulator of central tolerance. It plays an essential role in driving expression of tissue-specific antigens in the thymus and shaping the development of positively selected T-cells. Humans and mice with compromised or absent AIRE function have markedly variable phenotypes that include a range of autoimmune manifestations. Recent evidence suggests that this variability stems from cooperation of autoimmune susceptibilities involving both central and peripheral tolerance checkpoints. Here we discuss the broadening understanding of the factors that influence Aire expression,...
Source: Current Opinion in Immunology - October 21, 2017 Category: Allergy & Immunology Authors: Proekt I, Miller CN, Lionakis MS, Anderson MS Tags: Curr Opin Immunol Source Type: research

Biomarker-guided stratification of autoimmune patients for biologic therapy.
Abstract Autoimmunity results from an intersection of genetic and environmental factors that cause patient-specific perturbations in immune homeostasis. Defining autoimmunity-associated genetic factors has led to mechanistic insight into underlying etiologies, and the development of many biologic therapies that target the immune system. However, biomarker-informed pairing of patients with optimal biologic therapy is lacking. Here, we discuss platforms commonly used to find biomarkers that predict response to biologic therapy in autoimmunity and highlight recent biomarker discoveries. We also outline how the lack o...
Source: Current Opinion in Immunology - October 17, 2017 Category: Allergy & Immunology Authors: Ivison S, des Rosiers C, Lesage S, Rioux JD, Levings MK Tags: Curr Opin Immunol Source Type: research

Innate sensing of cancer's non-immunologic hallmarks.
Abstract A cancer mass consists of a complex composition of cancer cells, stromal cells, endothelial cells and also immune cells, which can represent more than half of the cellularity of a solid cancer. These immune cells become activated when they sense cancer antigens and stress ligands. Innate immune cells also detect various aspects of cellular stress that characterize a growing tumor mass. These key hallmarks of cellular stress are also detected by the cancer cell itself. In this review, we highlight studies that show that the cancer cell itself could be considered an 'innate cell' that senses and reacts to n...
Source: Current Opinion in Immunology - October 12, 2017 Category: Allergy & Immunology Authors: Seelige R, Searles S, Bui JD Tags: Curr Opin Immunol Source Type: research

Pathogenesis of infections in HIV-infected individuals: insights from primary immunodeficiencies.
Abstract Following infection with almost any given microorganism other than an emerging pathogen, only a minority of individuals develop life-threatening clinical disease, implying that these individuals have some form of immunodeficiency. A growing number of inherited and acquired immunodeficiencies have been deciphered over the last 50 years. HIV infection is probably the best-known acquired immunodeficiency. It emerged about 40 years ago and precipitates various severe infections, the occurrence of which is associated with a fall in circulating CD4(+) T cells. However, despite the strength of this correlation, ...
Source: Current Opinion in Immunology - October 6, 2017 Category: Allergy & Immunology Authors: Zhang Q, Frange P, Blanche S, Casanova JL Tags: Curr Opin Immunol Source Type: research

Have we pushed the needle for treatment of Type 1 diabetes?
Abstract Studies with immunologics have shown that the natural history of Type 1 diabetes can be modified. These studies have targeted key mediators of the disease and recent analyses, together with studies in preclinical models have identified mechanisms that may be involved in the clinical effects. Several issues remain including specificity of the interventions, adverse effects of the treatments, and duration of their effects. Future studies are likely to include more specific approaches with agents such as cell therapies with selected immune regulatory subsets, antigen specific therapies, and combinations of a...
Source: Current Opinion in Immunology - October 6, 2017 Category: Allergy & Immunology Authors: Naushad N, Perdigoto AL, Rui J, Herold KC Tags: Curr Opin Immunol Source Type: research

Novel immunologic mechanisms in eosinophilic esophagitis.
PMID: 28965008 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - September 28, 2017 Category: Allergy & Immunology Authors: Caldwell JM, Paul M, Rothenberg ME Tags: Curr Opin Immunol Source Type: research

Immunomodulation in multiple sclerosis: promises and pitfalls.
This article reviews the main mechanisms of MS immunopathogenesis, and the benefits, risks and challenges of immunomodulatory treatments for the disease. PMID: 28926740 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - September 16, 2017 Category: Allergy & Immunology Authors: Dendrou CA, Fugger L Tags: Curr Opin Immunol Source Type: research

Immune regulation by histamine and histamine-secreting bacteria.
Abstract Histamine is a biogenic amine with extensive effects on many immune cell types. Histamine and its four receptors (H1R-H4R) represent a complex system of immunoregulation with distinct effects dependent on receptor subtypes and their differential expression. In addition to mammalian cells, bacteria can also secrete histamine and the influence of microbiota-derived histamine on host immunological processes is only beginning to be described. However, it is clear that histamine-secreting microbes are present within the human gut microbiota and their levels are increased in asthma patients. Additional studies ...
Source: Current Opinion in Immunology - September 15, 2017 Category: Allergy & Immunology Authors: Barcik W, Wawrzyniak M, Akdis CA, O'Mahony L Tags: Curr Opin Immunol Source Type: research

Revisiting murine models for atopic dermatitis and psoriasis with multipolar cytokine axes.
Abstract Atopic dermatitis (AD) and psoriasis are one of the common skin diseases. Animal models are a powerful tool to analyze these diseases, which are complicated by multiple cytokine pathways. However, many discrepancies between the human diseases and murine models have been noticed. Therefore, investigators should be aware of the differences between the murine AD models and human AD when translating murine data to human skin diseases. This review highlights the differences between the inflammatory profiles between murine models and human diseases focusing on AD and psoriasis. PMID: 28915378 [PubMed - as ...
Source: Current Opinion in Immunology - September 12, 2017 Category: Allergy & Immunology Authors: Kabashima K, Nomura T Tags: Curr Opin Immunol Source Type: research

Immune mechanisms of food allergy and its prevention by early intervention.
Abstract The environmental factors driving the increase in food allergies are unclear and possibly involve dual exposure to allergens, microbiome-driven effects or other mechanisms. Until they can be better understood, early intervention aiming at establishing oral tolerance provides an effective way to decrease the window-of-risk when children may develop allergic sensitisation to foods due to the absence of a protective immune response. Thus, the recent LEAP (Learning Early About Peanut allergy) and LEAP-On studies achieved a high level of peanut allergy prevention by early introduction of peanuts in the infants...
Source: Current Opinion in Immunology - September 8, 2017 Category: Allergy & Immunology Authors: Turcanu V, Brough HA, Du Toit G, Foong RX, Marrs T, Santos AF, Lack G Tags: Curr Opin Immunol Source Type: research

Immune monitoring for precision medicine in allergy and asthma.
Abstract 'Precision Medicine' embodies the analyses of extensive data collected from patients and their environments to identify and apply patient-specific prophylactic strategies and medical treatments to improve clinical outcomes and healthcare cost-effectiveness. Many new methods have been developed for evaluating the activity of the human immune system. Such 'immune monitoring' approaches are now being used in studies of allergy and asthma in the hope of identifying better correlates of disease status, predictors of therapeutic outcomes, and potential side-effects of treatment. Together with analyses of family...
Source: Current Opinion in Immunology - September 6, 2017 Category: Allergy & Immunology Authors: Boyd SD, Hoh RA, Nadeau KC, Galli SJ Tags: Curr Opin Immunol Source Type: research

Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis.
Abstract CD4+ T cells have been long known to play an important role in the pathogenesis of rheumatoid arthritis (RA), but the specific cell populations and states that drive the disease have been challenging to identify with low dimensional single cell data and bulk assays. The advent of high dimensional single cell technologies-like single cell RNA-seq or mass cytometry-has offered promise to defining key populations, but brings new methodological and statistical challenges. Recent single cell profiling studies have revealed a broad diversity of cell types among CD4+ T cells, identifying novel populations that a...
Source: Current Opinion in Immunology - September 6, 2017 Category: Allergy & Immunology Authors: Fonseka CY, Rao DA, Raychaudhuri S Tags: Curr Opin Immunol Source Type: research