Sugar, fat, and protein: new insights into what T cells crave.
Abstract T cell activation and differentiation is a complex process that has evolved beyond the two-signal model to a number of varied and opposing inputs that must be interpreted to make a cell fate decision. While stimulation through the TCR, costimulatory, and cytokine receptors is required, metabolic signaling has emerged not only as an activation signal, but also one that can influence and shape differentiation. Recent findings have revealed unappreciated roles for glucose, fatty acids, and salt in the function of many T cell subsets. In this review, we will highlight the latest advances in the burgeoning fie...
Source: Current Opinion in Immunology - February 6, 2015 Category: Allergy & Immunology Authors: Delgoffe GM, Powell JD Tags: Curr Opin Immunol Source Type: research

Targeting the tumor vasculature to enhance T cell activity.
Abstract T cells play a critical role in tumor immune surveillance as evidenced by extensive mouse-tumor model studies as well as encouraging patient responses to adoptive T cell therapies and dendritic cell vaccines. It is well established that the interplay of tumor cells with their local cellular environment can trigger events that are immunoinhibitory to T cells. More recently it is emerging that the tumor vasculature itself constitutes an important barrier to T cells. Endothelial cells lining the vessels can suppress T cell activity, target them for destruction, and block them from gaining entry into the tumo...
Source: Current Opinion in Immunology - February 6, 2015 Category: Allergy & Immunology Authors: Lanitis E, Irving M, Coukos G Tags: Curr Opin Immunol Source Type: research

NLRs in plants.
Abstract Intracellular immune receptors with nucleotide-binding, leucine-rich domains (NLRs) are found in both plants and animals. Compared to animals, NLR-encoding gene families are expanded, more prevalent and have enriched diversity in higher plants. Strong host defense triggered by the recognition of specific pathogen effectors constitutes a major part of the plant immune response that has long been exploited to breed crops for enhanced resistance. Although the first plant NLR genes were cloned about 20 years ago, their signaling mechanisms remain obscure. Here we review recent progress in plant NLR studies, f...
Source: Current Opinion in Immunology - February 6, 2015 Category: Allergy & Immunology Authors: Li X, Kapos P, Zhang Y Tags: Curr Opin Immunol Source Type: research

The role of T cell receptor signaling thresholds in guiding T cell fate decisions.
Abstract Canonical T cell receptor signal transduction has been extensively studied and dissected in cell lines and primary lymphocytes. However, a static depiction of this signaling cascade fails to capture the complex and dynamic process by which individual T cells discriminate TCR:peptide-MHC affinity, then integrate signals over time to drive discrete cellular behaviors such as thymic selection, proliferation, and cytokine production. Recent technological advances have made it possible to study complex lymphocyte behavior on a single cell level and are revealing how T cells interpret information about affinity...
Source: Current Opinion in Immunology - February 5, 2015 Category: Allergy & Immunology Authors: Zikherman J, Au-Yeung B Tags: Curr Opin Immunol Source Type: research

Discovering protective CD8 T cell epitopes-no single immunologic property predicts it!
Abstract Once a burgeoning field of study, over the past decade or so, T cell epitope discovery has lost some luster. The contributory factors perchance are the general notion that any newly discovered epitope will reveal very little about an immune response and that knowledge of epitopes are less critical for vaccine design. Despite these notions, the breadth and depth of T cell epitopes derived from clinically important microbial agents of human diseases largely remain ill defined. We review here a flurry of recent reports that have rebirthed the field. These reports reveal that epitope discovery is an essential...
Source: Current Opinion in Immunology - February 5, 2015 Category: Allergy & Immunology Authors: Gilchuk P, Hill TM, Wilson JT, Joyce S Tags: Curr Opin Immunol Source Type: research

Sensing viral RNAs by Dicer/RIG-I like ATPases across species.
Abstract Induction of antiviral immunity in vertebrates and invertebrates relies on members of the RIG-I-like receptor and Dicer families, respectively. Although these proteins have different size and domain composition, members of both families share a conserved DECH-box helicase domain. This helicase, also known as a duplex RNA activated ATPase, or DRA domain, plays an important role in viral RNA sensing. Crystallographic and electron microscopy studies of the RIG-I and Dicer DRA domains indicate a common structure and that similar conformational changes are induced by dsRNA binding. Genetic and biochemical stud...
Source: Current Opinion in Immunology - February 3, 2015 Category: Allergy & Immunology Authors: Paro S, Imler JL, Meignin C Tags: Curr Opin Immunol Source Type: research

Immunological loss-of-function due to genetic gain-of-function in humans: autosomal dominance of the third kind.
Abstract All the human primary immunodeficiencies (PIDs) recognized as such in the 1950s were Mendelian traits and, whether autosomal or X-linked, displayed recessive inheritance. The first autosomal dominant (AD) PID, hereditary angioedema, was recognized in 1963. However, since the first identification of autosomal recessive (AR), X-linked recessive (XR) and AD PID-causing genes in 1985 (ADA; severe combined immunodeficiency), 1986 (CYBB, chronic granulomatous disease) and 1989 (SERPING1; hereditary angioedema), respectively, the number of genetically defined AD PIDs has increased more rapidly than that of any o...
Source: Current Opinion in Immunology - January 30, 2015 Category: Allergy & Immunology Authors: Boisson B, Quartier P, Casanova JL Tags: Curr Opin Immunol Source Type: research

What chickens would tell you about the evolution of antigen processing and presentation.
Abstract Outside of mammals, antigen processing and presentation have only been investigated in chickens. The chicken MHC is organized differently than mammals, allowing the co-evolution of polymorphic genes, with each MHC haplotype having a set of TAP1, TAP2 and tapasin alleles directed to high expression of a single classical class I molecule. However, the class I alleles vary in the size of peptide-binding repertoire, along with a suite of other properties. The salient features of the chicken MHC are found in many non-mammalian vertebrates, and are likely to have been set at the origin of the adaptive immune sy...
Source: Current Opinion in Immunology - January 24, 2015 Category: Allergy & Immunology Authors: Kaufman J Tags: Curr Opin Immunol Source Type: research

Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity.
Abstract Lipopolysaccharide (LPS) is the major component of Gram-negative bacteria cell wall. In innate immunity, extracellular LPS is recognized by Toll-like receptor 4 to stimulate cytokine transcription. Recent studies suggest a 'non-canonical inflammasome' that senses cytoplasmic LPS and activates caspase-11 in mouse macrophages. Unexpectedly, biochemical studies reveal that caspase-11 and its human orthologs caspase-4/caspase-5 are LPS receptors themselves. Direct LPS binding induces caspase-4/caspase-5/caspase-11 oligomerization and activation, triggering cell pyroptosis and anti-bacterial defenses. Caspase-...
Source: Current Opinion in Immunology - January 23, 2015 Category: Allergy & Immunology Authors: Yang J, Zhao Y, Shao F Tags: Curr Opin Immunol Source Type: research

The NAIP/NLRC4 inflammasomes.
Abstract Inflammasomes comprise a family of cytosolic multi-protein complexes that sense infection, or other threats, and initiate inflammation via the recruitment and activation of the Caspase-1 protease. Although the precise molecular mechanism by which most inflammasomes are activated remains a subject of considerable debate, the NAIP/NLRC4 subfamily of inflammasomes is increasingly well understood. A crystal structure of NLRC4 was recently reported, and a domain in NAIPs that recognizes bacterial ligands was identified. In addition, gain-of-function mutations in NLRC4 have been shown to cause an auto-inflammat...
Source: Current Opinion in Immunology - January 23, 2015 Category: Allergy & Immunology Authors: Vance RE Tags: Curr Opin Immunol Source Type: research

Designing chimeric antigen receptors to effectively and safely target tumors.
Abstract The adoptive transfer of T cells engineered to express artificial chimeric antigen receptors CARs) that target a tumor cell surface molecule has emerged as an exciting new approach for cancer immunotherapy. Clinical trials in patients with advanced B cell malignancies treated with CD19-specific CAR-modified T cells (CAR-T) have shown impressive antitumor efficacy, leading to optimism that this approach will be useful for treating common solid tumors. Because CAR-T cells recognize tumor cells independent of their expression of human leukocyte antigen (HLA) molecules, tumors that escape conventional T cells...
Source: Current Opinion in Immunology - January 23, 2015 Category: Allergy & Immunology Authors: Jensen MC, Riddell SR Tags: Curr Opin Immunol Source Type: research

The evolution of checkpoint blockade as a cancer therapy: what's here, what's next?
Abstract Unleashing the immune system to fight cancer has become one of the main treatment modalities since the anti-CTLA-4 antibody, ipilimumab was approved for patients with advanced melanoma in 2011. Pembrolizumab and nivolumab, two anti-PD-1 antibodies recently approved for the treatment of patients with metastatic melanoma, are being actively investigated for the treatment of multiple caners including lung, breast, bladder and renal cancers along with other anti-PD-1/L1 antibodies. Early results of combining of anti-CTLA-4 antibody and anti-PD-1 antibody treatment for advanced melanoma patients are showing im...
Source: Current Opinion in Immunology - January 23, 2015 Category: Allergy & Immunology Authors: Shin DS, Ribas A Tags: Curr Opin Immunol Source Type: research

Role of group 3 innate lymphoid cells in antibody production.
Abstract Innate lymphoid cells (ILCs) constitute a heterogeneous family of effector lymphocytes of the innate immune system that mediate lymphoid organogenesis, tissue repair, immunity and inflammation. The initial view that ILCs exert their protective functions solely during the innate phase of an immune response has been recently challenged by evidence indicating that ILCs shape adaptive immunity by establishing both contact-dependent and contact-independent interactions with multiple hematopoietic and non-hematopoietic cells, including B cells. Some of these interactions enhance antibody responses both systemic...
Source: Current Opinion in Immunology - January 23, 2015 Category: Allergy & Immunology Authors: Magri G, Cerutti A Tags: Curr Opin Immunol Source Type: research

TCR affinity for p/MHC formed by tumor antigens that are self-proteins: impact on efficacy and toxicity.
Abstract Recent studies have shown that the range of affinities of T cell receptors (TCRs) against non-mutated cancer peptide/class I complexes are lower than TCR affinities for foreign antigens. Raising the affinity of TCRs for optimal activity of CD8 T cells, and for recruitment of CD4 T cell activity against a class I antigen, provides opportunities for more robust adoptive T cell therapies. However, TCRs with enhanced affinities also risk increased reactivity with structurally related self-peptides, and off-target toxicities. Careful selection of tumor peptide antigens, in silico proteome screens, and in vitro...
Source: Current Opinion in Immunology - January 22, 2015 Category: Allergy & Immunology Authors: Stone JD, Harris DT, Kranz DM Tags: Curr Opin Immunol Source Type: research

Innate immune sensing of HIV infection.
Abstract The ability to sense infections is primordial to preserve organisms. Immune cells express pathogen sensors that induct innate and adaptive immune responses. Understanding how HIV-1 infection defeats these responses in most individuals remains an outstanding challenge. Since HIV-1 targets immune cells, innate immune sensors are remarkably positioned at the nexus of viral replication and immunity. Here, we discuss recent studies that have revealed innate sensing mechanisms of HIV-1 infection in plasmacytoid dendritic cells, monocyte-derived dendritic cells, monocyte-derived macrophages, and CD4+ T cells. Th...
Source: Current Opinion in Immunology - January 21, 2015 Category: Allergy & Immunology Authors: Silvin A, Manel N Tags: Curr Opin Immunol Source Type: research

Microbial strategies for antagonizing Toll-like-receptor signal transduction.
Abstract Within a few years of the discovery of Toll-like receptors (TLRs) and their role in innate immunity, viral and bacterial proteins were recognized to antagonize TLR signal transduction. Since then, as TLR signaling networks were unraveled, microbial systems have been discovered that target nearly every component within these pathways. However, recent findings as well as some notable exceptions promote the idea that more of these systems have yet to be discovered. For example, we know very little about microbial systems for directly targeting non-cytoplasmic portions of TLR signaling pathways, that is, the ...
Source: Current Opinion in Immunology - January 20, 2015 Category: Allergy & Immunology Authors: Rosadini CV, Kagan JC Tags: Curr Opin Immunol Source Type: research

Innate lymphoid cells: new insights into function and development.
Abstract Here, we illustrate the complexity of ILC subsets and discuss novel functions, focusing on emerging mechanisms of crosstalk with other immune cells and the microbiota. Furthermore, we highlight recent insights into the development of ILCs, including the common pathways they share as well as points of divergence between ILC groups and subsets. PMID: 25615701 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - January 20, 2015 Category: Allergy & Immunology Authors: Cortez VS, Robinette ML, Colonna M Tags: Curr Opin Immunol Source Type: research

MR1 presentation of vitamin B-based metabolite ligands.
Abstract The major histocompatibility complex class I-related molecule MR1 can bind a novel class of antigens, namely a family of related small organic vitamin B metabolites. When bound to MR1 these metabolites are presented to a population of innate-like T cells, mucosal-associated invariant T (MAIT) cells that express a semi-invariant T cell receptor (TCR). Several non-activating and activating MR1-restricted ligands have been described, which are the degradation products of, or intermediates of, vitamin B9 (folic acid) or vitamin B2 (riboflavin), respectively. The MAIT-activating intermediates of the riboflavin...
Source: Current Opinion in Immunology - January 17, 2015 Category: Allergy & Immunology Authors: McWilliam HE, Birkinshaw RW, Villadangos JA, McCluskey J, Rossjohn J Tags: Curr Opin Immunol Source Type: research

Suppression of antigen presentation by IL-10.
Abstract Regulated antigen presentation to immune cells determines the effectiveness of an immune response. IL-10 is an immunosuppressive cytokine that regulates immune responses by inhibiting the ability of APCs to present antigens to T cells in a variety of ways. The mechanisms of IL-10-mediated immunosuppression include interference in TLR-mediated or IFNγ-mediated dendritic cell (DC) and macrophage activation as well as direct induction of genes that suppress APC function. In this review we will discuss current studies exploring the molecular mechanisms by which IL-10 suppresses APC function. PMID: ...
Source: Current Opinion in Immunology - January 15, 2015 Category: Allergy & Immunology Authors: Mittal SK, Roche PA Tags: Curr Opin Immunol Source Type: research

Viral RNA detection by RIG-I-like receptors.
Abstract In higher vertebrates, recognition of the non-self signature of invading viruses by genome-encoded pattern recognition receptors initiates antiviral innate immunity. Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) detect viral RNA as a non-self pattern in the cytoplasm and activate downstream signaling. Detection of viral RNA also activates stress responses resulting in stress granule-like aggregates, which facilitate RLR-mediated antiviral immunity. Among the three RLR family members RIG-I and melanoma differentiation-associated gene 5 (MDA5) recognize distinct viral RNA species with differe...
Source: Current Opinion in Immunology - January 13, 2015 Category: Allergy & Immunology Authors: Yoneyama M, Onomoto K, Jogi M, Akaboshi T, Fujita T Tags: Curr Opin Immunol Source Type: research

Systems approaches to unravel innate immune cell diversity, environmental plasticity and functional specialization.
Abstract Innate immune cells are generated through central and peripheral differentiation pathways, and receive multiple signals from tissue microenvironment. The complex interplay between immune cell state and environmental signals is crucial for the adaptation and efficient response to pathogenic threats. Here, we discuss how systems biology approaches have brought global view and high resolution to the characterization of (1) immune cell diversity, (2) phenotypic, transcriptional and functional changes in response to environmental signals, (3) integration of multiple stimuli. We will mostly focus on systems lev...
Source: Current Opinion in Immunology - January 9, 2015 Category: Allergy & Immunology Authors: Soumelis V, Pattarini L, Michea P, Cappuccio A Tags: Curr Opin Immunol Source Type: research

Modulation of antigen presentation by intracellular trafficking.
Abstract Processing and loading of antigen into major histocompatibility complex molecules (MHC) occurs in specific intracellular compartments. Accessing MHC loading compartments requires trafficking via specific pathways, some of which have yet to be fully characterized. For MHC I, cross-presentation involves antigen trafficking to a specialised compartment. We review the features of this compartment and how it is accessed by different mechanisms of antigen capture and internalization. We also summarize advances in understanding how antigen efficiently accesses the MHC II loading compartment, with particular focu...
Source: Current Opinion in Immunology - January 8, 2015 Category: Allergy & Immunology Authors: Mintern JD, Macri C, Villadangos JA Tags: Curr Opin Immunol Source Type: research

Determinants of immunodominance for CD4 T cells.
Abstract The term immunodominance was originally defined as a restricted T cell response to a short peptide sequence derived from a given protein [1]. The question of what determines immunodominance has been a longstanding battle for the past two decades. Hundreds of papers have been written on different aspects of epitope selection during antigen processing documenting the complexity of the process. Antigen processing machinery involves several accessory molecules and chaperons coevolved with proteins of Major Histocompatibility Complex (MHC) molecules that each plays its part in epitope selection. These molecule...
Source: Current Opinion in Immunology - January 7, 2015 Category: Allergy & Immunology Authors: Kim A, Sadegh-Nasseri S Tags: Curr Opin Immunol Source Type: research

Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors.
Abstract Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and anti...
Source: Current Opinion in Immunology - January 7, 2015 Category: Allergy & Immunology Authors: Chester C, Marabelle A, Houot R, Kohrt HE Tags: Curr Opin Immunol Source Type: research

The roles of CRISPR-Cas systems in adaptive immunity and beyond.
Abstract Clustered regularly interspaced short palindromic repeats (CRISPR) and accompanying Cas proteins constitute the adaptive CRISPR-Cas immune system in bacteria and archaea. This DNA-encoded, RNA-mediated defense system provides sequence-specific recognition, targeting and degradation of exogenous nucleic acid. Though the primary established role of CRISPR-Cas systems is in bona fide adaptive antiviral defense in bacteria, a growing body of evidence indicates that it also plays critical functional roles beyond immunity, such as endogenous transcriptional control. Furthermore, benefits inherent to maintaining...
Source: Current Opinion in Immunology - January 6, 2015 Category: Allergy & Immunology Authors: Barrangou R Tags: Curr Opin Immunol Source Type: research

C-type lectins in immunity: recent developments.
Abstract C-type lectin receptors (CLRs) comprise a large superfamily of proteins, which recognise a diverse range of ligands, and are defined by the presence of at least one C-type lectin-like domain (CTLD). Of particular interest are the single extracellular CTLD-containing receptors of the 'Dectin-1' and 'Dectin-2' clusters, which associate with signalling adaptors or possess integral intracellular signalling domains. These CLRs have traditionally been associated with the recognition of fungi, but recent discoveries have revealed diverse and unexpected functions. In this review, we describe their newly identifie...
Source: Current Opinion in Immunology - December 29, 2014 Category: Allergy & Immunology Authors: Dambuza IM, Brown GD Tags: Curr Opin Immunol Source Type: research

Protein synthesis regulation, a pillar of strength for innate immunity?
e P Abstract Recognition of pathogen derived molecules by Pattern Recognition Receptors (PRR) induces the production of cytokines (i.e. type I interferons) that stimulate the surrounding cells to transcribe and translate hundreds of genes, in order to prevent further infection and organize the immune response. Here, we report on the rising matter that metabolism sensing and gene expression control at the level of mRNA translation, allow swift responses that mobilize host defenses and coordinate innate responses to infection. PMID: 25553394 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - December 29, 2014 Category: Allergy & Immunology Authors: Argüello RJ, Rodrigues CR, Gatti E, Pierre P Tags: Curr Opin Immunol Source Type: research

Defining dendritic cells.
Abstract Dendritic cells (DCs) are versatile controllers of the immune system, best known for their potent ability to initiate adaptive immunity. Traditionally, DCs have been defined on the basis of cell morphology, expression of specific markers and select functional attributes such as the ability to migrate to T cell areas of secondary lymphoid organs and activate T lymphocytes. However, such properties are not qualitative and often change in conditions of inflammation or infection. Phenotypic-based and function-based definitions can therefore lead to difficulties in cell identification. Here we review other app...
Source: Current Opinion in Immunology - December 2, 2014 Category: Allergy & Immunology Authors: Schraml BU, Reis E Sousa C Tags: Curr Opin Immunol Source Type: research

Genetics of immune-mediated disorders: from genome-wide association to molecular mechanism.
Abstract Genetic association studies have identified not only hundreds of susceptibility loci to immune-mediated diseases but also pinpointed causal amino-acid variants of HLA genes that contribute to many autoimmune reactions. Majority of non-HLA genetic variants are located within non-coding regulatory region. Expression QTL studies have shown that these variants affect disease mainly by regulating gene expression. We discuss recent findings on shared genetic loci between infectious and immune-mediated diseases and provide potential clues to explore genetic associations in the context of these infectious agents....
Source: Current Opinion in Immunology - December 1, 2014 Category: Allergy & Immunology Authors: Kumar V, Wijmenga C, Xavier RJ Tags: Curr Opin Immunol Source Type: research

I-L-C-2 it: type 2 immunity and group 2 innate lymphoid cells in homeostasis.
Abstract Innate type 2 immune cells are activated in response to helminths, allergens, and certain types of proteases and particulates. Recently, innate type 2 immune pathways have also been implicated in protective host responses to homeostatic perturbations, such as metabolic dysfunction, atherosclerosis, and tissue injury. In this context, innate type 2 cytokines stimulate local tissues, recruit eosinophils, and alternatively activate macrophages to restore homeostasis. As the major source of innate interleukin (IL)-5 and IL-13, group 2 innate lymphoid cells are positioned to initiate and maintain homeostatic t...
Source: Current Opinion in Immunology - December 1, 2014 Category: Allergy & Immunology Authors: von Moltke J, Locksley RM Tags: Curr Opin Immunol Source Type: research

The contribution of natural selection to present-day susceptibility to chronic inflammatory and autoimmune disease.
Abstract Chronic inflammatory and autoimmune diseases have been the focus of many genome-wide association studies (GWAS) because they represent a significant cause of illness and morbidity, and many are heritable. Almost a decade of GWAS studies suggests that the pathological inflammation associated with these diseases is controlled by a limited number of networked immune system genes. Chronic inflammatory and autoimmune diseases are enigmatic from an evolutionary perspective because they exert a negative affect on reproductive fitness. The persistence of these conditions may be partially explained by the importan...
Source: Current Opinion in Immunology - December 1, 2014 Category: Allergy & Immunology Authors: Brinkworth JF, Barreiro LB Tags: Curr Opin Immunol Source Type: research

Cellular and molecular pathways through which commensal bacteria modulate sensitization to dietary antigens.
Abstract Food allergies are a growing public health concern. The rapidly increasing prevalence of allergic disease cannot be explained by genetic variation alone, suggesting a role for gene-by-environment interactions. The bacteria that colonize barrier surfaces, often referred to as the commensal microbiota, are dramatically affected by environmental factors and have a major impact on host health and homeostasis. Increasing evidence suggests that alterations in the composition of the microbiota, caused by factors such as antibiotic use and diet, are contributing to increased sensitization to dietary antigens. Thi...
Source: Current Opinion in Immunology - December 1, 2014 Category: Allergy & Immunology Authors: Feehley T, Nagler CR Tags: Curr Opin Immunol Source Type: research

Genetics of systemic lupus erythematosus: immune responses and end organ resistance to damage.
Abstract Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disorder. Considerable progress has been made to delineate the genetic control of this complex disorder. In this review, selected aspects of human and mouse genetics related to SLE are reviewed with emphasis on genes that contribute to both innate and adaptive immunity and to genes that contribute directly to susceptibility to end organ damage. It is concluded that the interactions among these two major pathways will provide further insight into the pathogenesis of SLE. An interactive model of the two major pathways is proposed without...
Source: Current Opinion in Immunology - December 1, 2014 Category: Allergy & Immunology Authors: Dai C, Deng Y, Quinlan A, Gaskin F, Tsao BP, Fu SM Tags: Curr Opin Immunol Source Type: research

Immunodeficiency and immune dysregulation associated with proximal defects of T cell receptor signaling.
Abstract Engagement of the TCR/CD3 complex triggers a cascade of events that result in T lymphocyte activation and promote positive and negative selection of thymocytes, T lymphocyte migration and effector functions, development and activation of regulatory T cells. Gene mutations that abrogate early TCR signaling are associated with profound abnormalities of T lymphocyte development and function both in humans and in mice, causing susceptibility to severe infections since early in life. In recent years, a growing number of genetic defects have been discovered that reduce, but do not completely abrogate proximal T...
Source: Current Opinion in Immunology - December 1, 2014 Category: Allergy & Immunology Authors: Notarangelo LD Tags: Curr Opin Immunol Source Type: research

Role of viruses and bacteria-virus interactions in autoimmunity.
Abstract A potential role for viral and bacterial-viral interactions in the pathogenesis of autoimmune disease has been long recognized. Recently, intensive investigation has begun to decipher interactions between specific microbes with the host that contribute toward autoimmunity. This work has primarily focused on known viral and bacterial pathogens. A major challenge is to determine the role of bacteria that are typically considered as commensals as well as chronic viruses. Furthermore, equally challenging is to prove causality given the potential complexity of microbe-microbe interactions. Important initial co...
Source: Current Opinion in Immunology - December 1, 2014 Category: Allergy & Immunology Authors: Steed AL, Stappenbeck TS Tags: Curr Opin Immunol Source Type: research

Dermal group 2 innate lymphoid cells in atopic dermatitis and allergy.
Abstract Type 2 immune responses in the skin cause a variety of pathologies, including urticaria and atopic dermatitis. Traditionally, CD4(+) helper T cells have been implicated in the pathogenesis of these conditions. However, recently a new player, the group 2 innate lymphoid (ILC2) cell, has emerged as an important contributor to skin allergies. In this review, we summarize our current knowledge of the role ILC2 cells play in the physiology and pathology of mouse and human skin. PMID: 25459002 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - December 1, 2014 Category: Allergy & Immunology Authors: Roediger B, Kyle R, Le Gros G, Weninger W Tags: Curr Opin Immunol Source Type: research

The role of ILC2 in pathology of type 2 inflammatory diseases.
Abstract Group 2 innate lymphoid cells (ILC2) which are strategically interspersed throughout barrier surfaces are important regulators of type 2 immune reactions, particularly against helminthic parasites. ILC2 are also involved in tissue homeostasis and repair. Studies in a variety of animal models have demonstrated that when dysregulated or chronically activated, ILC2 can contribute to the pathology of allergic inflammatory diseases such as allergic asthma and atopic dermatitis. Here we discuss new findings of the cross talk of ILC2 with other hematopoietic cells, in particular T cells, and review recent inform...
Source: Current Opinion in Immunology - December 1, 2014 Category: Allergy & Immunology Authors: Bernink JH, Germar K, Spits H Tags: Curr Opin Immunol Source Type: research

Self-DNA, STING-dependent signaling and the origins of autoinflammatory disease.
Abstract Self-DNA has long been considered a key cause of inflammatory and autoimmune disease, although the exact origin and general mechanisms of action have remained to be elucidated. Recently, new insight has been gained into our understanding of those innate immune pathways and sensors that are responsible for instigating self-DNA triggered autoinflammatory events in the cell. One such sensor referred to as STING (for stimulator of interferon genes) has been found to be seminal for controlling cytosolic-DNA induced cytokine production, and may be responsible for a wide variety of inflammatory diseases includin...
Source: Current Opinion in Immunology - December 1, 2014 Category: Allergy & Immunology Authors: Ahn J, Barber GN Tags: Curr Opin Immunol Source Type: research

The nature of self for T cells-a systems-level perspective.
Abstract T-cell development and function are regulated by MHC-associated self peptides, collectively referred to as the immunopeptidome. Large-scale mass spectrometry studies have highlighted three key features of the immunopeptidome. First, it is not a mirror of the proteome or the transcriptome, and its content cannot be predicted with currently available bioinformatic tools. Second, the immunopeptidome is more plastic than previously anticipated, and is molded by several cell-intrinsic and cell-extrinsic factors. Finally, the complexity of the immunopeptidome goes beyond the 20-amino acids alphabet encoded in t...
Source: Current Opinion in Immunology - November 15, 2014 Category: Allergy & Immunology Authors: Granados DP, Laumont CM, Thibault P, Perreault C Tags: Curr Opin Immunol Source Type: research

Editorial overview: Allergy and hypersensitivity.
PMID: 25456768 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - November 4, 2014 Category: Allergy & Immunology Authors: Sperling AI, Ansel KM Tags: Curr Opin Immunol Source Type: research

Editorial overview: Autoimmunity.
PMID: 25456769 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - November 1, 2014 Category: Allergy & Immunology Authors: Jabri B, Terhorst C Tags: Curr Opin Immunol Source Type: research

Type I interferonopathies: Mendelian type I interferon up-regulation.
Abstract The concept of grouping Mendelian disorders associated with an up-regulation of type I interferon has only recently been suggested. Here we discuss the progress being made in the delineation and understanding of this novel set of inborn errors of immunity, the human type I interferonopathies. PMID: 25463593 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - October 30, 2014 Category: Allergy & Immunology Authors: Crow YJ Tags: Curr Opin Immunol Source Type: research

Hepatic immune regulation by stromal cells.
Abstract A metabolic organ, the liver also has a central role in tolerance induction. Stromal cells lining the hepatic sinusoids, such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), are the first liver cells to encounter gut-derived and systemic antigens, thereby shaping local and systemic tolerance. Recent studies have demonstrated that stromal cells can modulate immune responses by antigen-dependent and independent mechanisms. Stromal cells interfere with the function of other antigen-presenting cells (APCs) and induce non-responsive T cells as well as regulatory T cells and mye...
Source: Current Opinion in Immunology - October 28, 2014 Category: Allergy & Immunology Authors: Schildberg FA, Sharpe AH, Turley SJ Tags: Curr Opin Immunol Source Type: research

Distinct dendritic cell subsets actively induce Th2 polarization.
Abstract The mechanisms by which dendritic cells induce Th2 polarization (DC(Th2) cells) have been controversial. Many have argued that DC(Th2) cells are not a distinct functional DC subset, but rather, DC-induced polarization of Th2 cells is a default pathway that occurs in the absence of inflammatory signals leading to DC-induced polarization of Th1/Th17 cells. However, recent studies demonstrate that distinct subsets of tissue DCs actively polarize Th2 cells after stimulation with type-2 inducing stimuli. DC(Th2) cells development is marked by the upregulation of specific transcription factors, cell surface mol...
Source: Current Opinion in Immunology - October 4, 2014 Category: Allergy & Immunology Authors: Tjota MY, Sperling AI Tags: Curr Opin Immunol Source Type: research

Inflammasome activation in response to dead cells and their metabolites.
Abstract Cell death cannot go unnoticed. It demands that the surrounding cells clear away the corpses in a manner appropriate to the type of cell death. Dying cells represent a threat to the body that should be eliminated by the host immune response. Inflammasome activation followed by IL-1alpha release and IL-1beta maturation is crucial for tackling pathological conditions, including infections, whereas inflammasome activation precedes inflammatory pyroptotic cell death. On the other hand, recent studies have shown that the inflammasome plays an important role in the pathogenesis of metabolic diseases, including ...
Source: Current Opinion in Immunology - October 1, 2014 Category: Allergy & Immunology Authors: Kono H, Kimura Y, Latz E Tags: Curr Opin Immunol Source Type: research

Mina: a Th2 response regulator meets TGFβ
Mina: a Th2 response regulator meets TGFβ Curr Opin Immunol. 2014 Oct 1;31C:38-43 Authors: Pillai MR, Lian S, Bix M Abstract The JmjC protein Mina is an important immune response regulator. Classical forward genetics first discovered its immune role in 2009 in connection with the development of T helper 2 (Th2) cells. This prompted investigation into Mina's role in the two best-studied contexts where Th2 responses are essential: atopic asthma and helminth expulsion. In work focused on a mouse model of atopic asthma, Mina deficiency was found to ameliorate airway hyper-resistance and pulmonary inf...
Source: Current Opinion in Immunology - October 1, 2014 Category: Allergy & Immunology Authors: Pillai MR, Lian S, Bix M Tags: Curr Opin Immunol Source Type: research

IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy.
Abstract IL-33 is a nuclear cytokine from the IL-1 family constitutively expressed in epithelial barrier tissues and lymphoid organs, which plays important roles in type-2 innate immunity and human asthma. Recent studies indicate that IL-33 induces production of large amounts of IL-5 and IL-13 by group 2 innate lymphoid cells (ILC2s), for initiation of allergic inflammation shortly after exposure to allergens or infection with parasites or viruses. IL-33 appears to function as an alarmin (alarm signal) rapidly released from producing cells upon cellular damage or cellular stress. In this review, we discuss the cel...
Source: Current Opinion in Immunology - September 29, 2014 Category: Allergy & Immunology Authors: Cayrol C, Girard JP Tags: Curr Opin Immunol Source Type: research

Editorial Overview: Immunogenetics and transplantation: Bringing evolution and genomics to human immunology.
PMID: 25240536 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - September 17, 2014 Category: Allergy & Immunology Authors: Barreiro LB, Quintana-Murci L Tags: Curr Opin Immunol Source Type: research

Editorial overview: Special section: Effects of endogenous immune stimulants: From a defence system against infection to a homeostatic mechanism linking metabolism with inflammation.
PMID: 25224931 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - September 12, 2014 Category: Allergy & Immunology Authors: Latz E, Miyake K Tags: Curr Opin Immunol Source Type: research

Molecular mechanisms for contribution of MHC molecules to autoimmune diseases.
Abstract It will soon be 50 years since the first MHC associations with human disease were described. These seminal studies opened a flourishing area of research, yet much remains to be discovered. Genome-wide association studies of autoimmune diseases have demonstrated that the MHC region has effect sizes that supersede those for any non-MHC locus for most diseases. Thus, an understanding of how particular MHC alleles confer susceptibility will be essential for a comprehensive understanding of autoimmune disease pathogenesis. Here we review recent exciting findings in this important field. PMID: 25216261 [Pu...
Source: Current Opinion in Immunology - September 9, 2014 Category: Allergy & Immunology Authors: Sollid LM, Pos W, Wucherpfennig KW Tags: Curr Opin Immunol Source Type: research