Preserving immune homeostasis with A20.
Abstract A20/TNFAIP3 is a TNF induced gene that plays a profound role in preserving cellular and organismal homeostasis (Lee, et al., 2000; Opipari etal., 1990). This protein has been linked to multiple human diseases via genetic, epigenetic, and an emerging series of patients with mono-allelic coding mutations. Diverse cellular functions of this pleiotropically expressed protein include immune-suppressive, anti-inflammatory, and cell protective functions. The A20 protein regulates ubiquitin dependent cell signals; however, the biochemical mechanisms by which it performs these functions is surprisingly complex. De...
Source: Advances in Immunology - November 17, 2020 Category: Allergy & Immunology Authors: Razani B, Malynn BA, Ma A Tags: Adv Immunol Source Type: research

Unexplored horizons of cDC1 in immunity and tolerance.
Abstract Dendritic cells are a specialized subset of hematopoietic cells essential for mounting immunity against tumors and infectious disease as well as inducing tolerance for maintenance of homeostasis. DCs are equipped with number of immunoregulatory or stimulatory molecules that interact with other leukocytes to modulate their functions. Recent advances in DC biology identified a specific role for the conventional dendritic cell type 1 (cDC1) in eliciting cytotoxic CD8+ T cells essential for clearance of tumors and infected cells. The critical role of this subset in eliciting immune responses or inducing toler...
Source: Advances in Immunology - November 17, 2020 Category: Allergy & Immunology Authors: Balan S, Radford KJ, Bhardwaj N Tags: Adv Immunol Source Type: research

IgE and mast cells: The endogenous adjuvant.
Abstract Mast cells and IgE are most familiar as the effectors of type I hypersensitivity reactions including anaphylaxis. It is becoming clear however that this pair has important immunomodulatory effects on innate and adaptive cells of the immune system. In this purview, they act as endogenous adjuvants to ignite evolving immune responses, promote the transition of allergic disease into chronic illness and disrupt the development of active mechanisms of tolerance to ingested foods. Suppression of IgE-mediated mast cell activation can be exerted by molecules targeting IgE, FcɛRI or signaling kinases including Sy...
Source: Advances in Immunology - November 17, 2020 Category: Allergy & Immunology Authors: El Ansari YS, Kanagaratham C, Lewis OL, Oettgen HC Tags: Adv Immunol Source Type: research

Histone deacetylases as targets in autoimmune and autoinflammatory diseases.
Abstract Reversible lysine acetylation of histones is a key epigenetic regulatory process controlling gene expression. Reversible histone acetylation is mediated by two opposing enzyme families: histone acetyltransferases (HATs) and histone deacetylases (HDACs). Moreover, many non-histone targets of HATs and HDACs are known, suggesting a crucial role for lysine acetylation as a posttranslational modification on the cellular proteome and protein function far beyond chromatin-mediated gene regulation. The HDAC family consists of 18 members and pan-HDAC inhibitors (HDACi) are clinically used for the treatment of cert...
Source: Advances in Immunology - September 29, 2020 Category: Allergy & Immunology Authors: Hamminger P, Rica R, Ellmeier W Tags: Adv Immunol Source Type: research

The role of NK cell as central communicators in cancer immunity.
JP Abstract Natural killer (NK) cells are innate immune cells critically involved in the control of cancer. Their important role in cancer immunity reflects the ability of NK cells to recognize malignant cells through an array of germline-encoded receptors expressed on their surface, enabling NK cells to detect and rapidly kill tumor cells through targeted cytotoxicity. In addition to their cytotoxic activity, NK cells fulfill a fundamental and often underappreciated role in the local orchestration of cancer immunity through their ability to communicate with innate and adaptive immune cells within the tumor micro...
Source: Advances in Immunology - September 29, 2020 Category: Allergy & Immunology Authors: Bald T, Pedde AM, Corvino D, Böttcher JP Tags: Adv Immunol Source Type: research

Mechanism and regulation of class switch recombination by IgH transcriptional control elements.
Abstract Class switch recombination (CSR) plays an important role in humoral immunity by generating antibodies with different effector functions. CSR to a particular antibody isotype is induced by external stimuli, and occurs between highly repetitive switch (S) sequences. CSR requires transcription across S regions, which generates long non-coding RNAs and secondary structures that promote accessibility of S sequences to activation-induced cytidine deaminase (AID). AID initiates DNA double-strand breaks (DSBs) intermediates that are repaired by general DNA repair pathways. Switch transcription is controlled by va...
Source: Advances in Immunology - September 29, 2020 Category: Allergy & Immunology Authors: Oudinet C, Braikia FZ, Dauba A, Khamlichi AA Tags: Adv Immunol Source Type: research

Transcriptional regulation of natural killer cell development and maturation.
Abstract Natural killer cells are lymphocytes that respond rapidly to intracellular pathogens or cancer/stressed cells by producing pro-inflammatory cytokines or chemokines and by killing target cells through direct cytolysis. NK cells are distinct from B and T lymphocytes in that they become activated through a series of broadly expressed germ line encoded activating and inhibitory receptors or through the actions of inflammatory cytokines. They are the founding member of the innate lymphoid cell family, which mirror the functions of T lymphocytes, with NK cells being the innate counterpart to CD8 T lymphocytes. ...
Source: Advances in Immunology - April 25, 2020 Category: Allergy & Immunology Authors: Kee BL, Morman RE, Sun M Tags: Adv Immunol Source Type: research

Homeostatic and pathogenic roles of PI3K δ in the human immune system.
Homeostatic and pathogenic roles of PI3Kδ in the human immune system. Adv Immunol. 2020;146:109-137 Authors: Sogkas G, Adriawan IR, Dubrowinskaja N, Atschekzei F, Schmidt RE Abstract Phosphoinositide 3-kinase delta (PI3Kδ) mediates signaling transduction downstream of diverse immune receptors, including the T cell receptor (TCR), the B cell receptor (BCR), costimulatory molecules and cytokine receptors. Our understanding of the role of PI3Kδ in the immune system comes primarily from mice, and especially from the consequences of pharmacological inhibition of PI3Kδ in mouse model...
Source: Advances in Immunology - April 25, 2020 Category: Allergy & Immunology Authors: Sogkas G, Adriawan IR, Dubrowinskaja N, Atschekzei F, Schmidt RE Tags: Adv Immunol Source Type: research

Friend or foe? Lactobacillus in the context of autoimmune disease.
Abstract Over the last decade, the interplay between the gut microbiota, the consortium of intestinal microbes that colonizes intestinal mucosal barriers, and its host immune system has been increasingly better understood. Disruption of the delicate balance between beneficial and pathogenic commensals, known as dysbiosis, contributes to a variety of chronic immunologic and metabolic diseases. Complicating this paradigm are bacterial strains that can operate paradoxically both as instigators and attenuators of inflammatory responses, depending on host background. Here, we review the role of several strains in the g...
Source: Advances in Immunology - April 25, 2020 Category: Allergy & Immunology Authors: Fine RL, Mubiru DL, Kriegel MA Tags: Adv Immunol Source Type: research

Unraveling the mysteries of plasma cells.
HM Abstract Antibody-secreting plasma cells are the central pillars of humoral immunity. They are generated in a fundamental cellular restructuring process from naive B cells upon contact with antigen. This outstanding process is guided and controlled by a complex transcriptional network accompanied by a fascinating morphological metamorphosis, governed by the combined action of Blimp-1, Xbp-1 and IRF-4. The survival of plasma cells requires the intimate interaction with a specific microenvironment, consisting of stromal cells and cells of hematopoietic origin. Cell-cell contacts, cytokines and availability of me...
Source: Advances in Immunology - April 25, 2020 Category: Allergy & Immunology Authors: Schuh W, Mielenz D, Jäck HM Tags: Adv Immunol Source Type: research

Deciphering the pathways to antiviral innate immunity and inflammation.
Abstract The antiviral innate immune and inflammatory responses are critical for host defense against viral infection. How these antiviral responses are initiated and regulated has been intensively investigated. Viral nucleic acids are sensed by pattern-recognition receptors (PRRs), which trigger various signaling pathways by utilizing distinct adaptor proteins, kinases and regulatory proteins. These pathways lead to activation of the transcriptional factors NF-κB and IRF3 and ultimate induction of antiviral effector proteins including type I interferons (IFNs), TNF and IL-1β, which are critical mediato...
Source: Advances in Immunology - February 23, 2020 Category: Allergy & Immunology Authors: Yang Q, Shu HB Tags: Adv Immunol Source Type: research

Metabolic regulation of innate immunity.
Abstract Immune responses are often accompanied by radical changes of cellular metabolism of immune cells. On the other hand, an ever increasing number of metabolic pathways and products have been found to possess immune regulatory functions. The field of immunometabolism that investigates the interplay between metabolism and immunity has developed rapidly during the past decade. In this chapter, we attempt to summarize the recent progresses by scientists in China on metabolic regulation of innate immunity from the following three perspectives: metabolic regulation of myeloid cell functions, metabolic adaptations ...
Source: Advances in Immunology - February 23, 2020 Category: Allergy & Immunology Authors: Liang S, Ji L, Kang L, Hu X Tags: Adv Immunol Source Type: research

Regulation of MHC class I-independent NK cell education by SLAM family receptors.
Abstract Seven members of signaling lymphocytic activation molecule (SLAM) family receptors (SFRs) are ubiquitously expressed on hematopoietic cells and they play critical roles in immune cell differentiation and activation. The engagement of these receptors transmits intracellular signaling mainly by recruiting SLAM-associated protein (SAP) and its related adaptors, EWS-FLI1-activated transcript-2 (EAT-2) and EAT-2-related transducer (ERT). The critical roles of SFRs and SAP-family adaptors are highlighted by the discovery that SAP is mutated in human X-linked lymphoproliferative (XLP1) disease in which the conta...
Source: Advances in Immunology - February 23, 2020 Category: Allergy & Immunology Authors: Chen S, Li D, Wang Y, Li Q, Dong Z Tags: Adv Immunol Source Type: research

Metalloimmunology: The metal ion-controlled immunity.
Abstract Metals are essential components in all forms of life required for the function of nearly half of all enzymes and are critically involved in virtually all fundamental biological processes. Especially, the transition metals iron (Fe), zinc (Zn), manganese (Mn), nickel (Ni), copper (Cu) and cobalt (Co) are crucial micronutrients known to play vital roles in metabolism as well due to their unique redox properties. Metals carry out three major functions within metalloproteins: to provide structural support, to serve as enzymatic cofactors, and to mediate electron transportation. Metal ions are also involved in...
Source: Advances in Immunology - February 23, 2020 Category: Allergy & Immunology Authors: Wang C, Zhang R, Wei X, Lv M, Jiang Z Tags: Adv Immunol Source Type: research

Tissue-resident NK cells and other innate lymphoid cells.
Abstract Natural killer (NK) cells are important innate effectors for their defense against pathogens and tumors without the need of prior sensitization. Along with the growing understanding of basic NK cell biology, it has been widely accepted that NK cells are a heterogeneous population of innate lymphoid cell (ILC) family. Apart from the conventional NK cell (cNK) subset that circulates throughout the body, some non-lymphoid tissues contain tissue-resident NK (trNK) cell subsets, and the composition of NK cell subsets varies greatly with different locations. Except for cNK cells, other ILCs are known as tissue-...
Source: Advances in Immunology - February 23, 2020 Category: Allergy & Immunology Authors: Zhou J, Tian Z, Peng H Tags: Adv Immunol Source Type: research

The strategies of targeting the NLRP3 inflammasome to treat inflammatory diseases.
Abstract The NLRP3 inflammasome is a cytoplasmic multiprotein complex, the assembly of which can be initiated in response to various exogenous or endogenous danger signals. Excessive activation of the NLRP3 inflammasome has been implicated in the pathogenesis of a wide variety of human inflammatory diseases, suggesting that the NLRP3 inflammasome is a potential target for the treatment of these diseases. However, clinical drugs targeting the NLRP3 inflammasome are still not available. Recent data have elucidated the different signaling pathways or events that can control NLRP3 inflammasome activation and have prov...
Source: Advances in Immunology - February 23, 2020 Category: Allergy & Immunology Authors: Jiang H, Gong T, Zhou R Tags: Adv Immunol Source Type: research

Fine-tuning of antiviral innate immunity by ubiquitination.
Abstract The innate immune system represents the first defense line of the host following viral infection. The infection triggers the recognition of pathogen-associated molecular patterns (PAMPs) from the viruses by pattern recognition receptors (PRRs) of the host cell. The interaction between viral PAMPs and PRRs evokes a sophisticated signal transduction system and eventually promotes the expression of type I interferons (IFNs) and proinflammatory cytokines. Ubiquitination plays an indispensable role in fine-tuning almost every single step of this signaling cascade given on its versatile functions. Ubiquitin lig...
Source: Advances in Immunology - February 23, 2020 Category: Allergy & Immunology Authors: Zheng Y, Gao C Tags: Adv Immunol Source Type: research

Thymocyte selection: From signaling to epigenetic regulation.
Abstract During thymocyte development at the double positive stage, thymocytes are subjected to a TCR quality check process termed "thymocyte selection." TCRs with proper binding capabilities to MHC molecules (with self-peptide) are able to transduce cell survival signals and allow the continuing of development to single positive T cells. It has been known that TCRs in DP cells can transduce signals with higher efficiency than peripheral mature T cells, even though they share most of the signaling components. Recent studies have revealed some thymocyte-specific signaling modulators including Themis and T...
Source: Advances in Immunology - November 10, 2019 Category: Allergy & Immunology Authors: Lyu J, Wang L, Lu L Tags: Adv Immunol Source Type: research

Molecular mechanisms of T helper 17 cell differentiation: Emerging roles for transcription cofactors.
Abstract T helper 17 (Th17) cells, characterized by secretion of IL-17 and IL-17F, are a specialized CD4+ effector T cell lineage that not only facilitates host defense against pathogen infection and maintenance of mucosal barrier, but also potently induces tissue inflammation and autoimmune diseases. Since its discovery in 2005, the developmental program of Th17 cells has been characterized, which involves a number of key cytokines, transcription factors and multiple layers of epigenetic modifications. However, how these mechanisms integrate into the complex regulatory network in Th17 cells has not been well defi...
Source: Advances in Immunology - November 10, 2019 Category: Allergy & Immunology Authors: Jiang Y, Wang X, Dong C Tags: Adv Immunol Source Type: research

T cell immune response within B-cell follicles.
Abstract B-cell follicle represents a functionally dynamic microstructure within second lymphoid tissues, predominantly consisting of B cells, follicular T cells and DCs. Through intimate interactions with cognate B cells, follicular helper T cells (Tfh) initiate and facilitate germinal center (GC) reactions by providing signals required for producing high-affinity antibodies, as well as for the generation of long-lived antibody-secreting plasma cells and memory B cells. Concomitantly, germinal center reaction needs to be fine controlled to avoid autoimmunity or B-cell malignancies. Among immune cells residing in ...
Source: Advances in Immunology - November 10, 2019 Category: Allergy & Immunology Authors: Huang Q, Xu L, Ye L Tags: Adv Immunol Source Type: research

Autoimmune diseases in China.
Abstract Autoimmune diseases, such as rheumatoid arthritis, systematic lupus erythematosus and Sjögren's syndrome, are a group of diseases characterized by the activation of immune cells and excessive production of autoantibodies. Although the pathogenesis of these diseases is still not completely understood, studies have shown that multiple factors including genetics, environment and immune responses play important roles in the development and progression of the diseases. In China, there are great achievements in the mechanisms of autoimmune diseases during the last decades. These studies provide new insight...
Source: Advances in Immunology - November 10, 2019 Category: Allergy & Immunology Authors: Li R, Sun X, Liu X, Yang Y, Li Z Tags: Adv Immunol Source Type: research

Understanding tumor-infiltrating lymphocytes by single cell RNA sequencing.
Abstract The clinical success of immune checkpoint blockade provides great hope for curing cancers. However, the patient responses are not even. Precise understanding of tumor immunity is necessary to improving the current cancer immunotherapies and to developing new treatment options. Here we applied full-length single cell RNA-seq (scRNA-seq) to three cancer types and provide a comprehensive single T cell data resource for understanding various characteristics of tumor-infiltrating T cells. We also developed an analytical framework named as STARTRAC to quantitatively characterize the dynamic properties of variou...
Source: Advances in Immunology - November 10, 2019 Category: Allergy & Immunology Authors: Ren X, Zhang Z Tags: Adv Immunol Source Type: research

B cell mechanosensing: A mechanistic overview.
Abstract B cells are essential to the adaptive immune system for providing the humoral immunity against cohorts of pathogens. The presentation of antigen to the B cell receptor (BCR) leads to the initiation of B cell activation, which is a process sensitive to the stiffness features of the substrates presenting the antigens. Mechanosensing of the B cells, potentiated through BCR signaling and the adhesion molecules, efficiently regulates B cell activation, proliferation and subsequent antibody responses. Defects in sensing of the antigen-presenting substrates can lead to the activation of autoreactive B cells in a...
Source: Advances in Immunology - November 10, 2019 Category: Allergy & Immunology Authors: Shaheen S, Wan Z, Haneef K, Zeng Y, Jing W, Liu W Tags: Adv Immunol Source Type: research

Ionic protein-lipid interactions at the plasma membrane regulate the structure and function of immunoreceptors.
Abstract Adaptive lymphocytes express a panel of immunoreceptors on the cell surface. Phospholipids are the major components of cell membranes, but they have functional roles beyond forming lipid bilayers. In particular, acidic phospholipids forming microdomains in the plasma membrane can ionically interact with proteins via polybasic sequences, which can have functional consequences for the protein. We have shown that negatively charged acidic phospholipids can interact with positively charged juxtamembrane polybasic regions of immunoreceptors, such as TCR-CD3, CD28 and IgG-BCR, to regulate protein structure and ...
Source: Advances in Immunology - November 10, 2019 Category: Allergy & Immunology Authors: Li H, Yan C, Guo J, Xu C Tags: Adv Immunol Source Type: research

Non-canonical Hippo signaling regulates immune responses.
Abstract The Hippo signaling pathway has been shown to play a pivotal role in controlling organ size and maintaining tissue homeostasis in multiple organisms ranging from Drosophila to mammals. Recently, we and others have demonstrated that Hippo signaling is also essential for maintaining the immune system homeostasis. Unlike the canonical Mst-Lats-Yap signal pathway, which controls tissue growth during development and regeneration, most studies regarding Hippo signaling in immune regulation is focusing in Mst1/2, the core kinases of Hippo signaling, cross-talking with other signaling pathways in various immune c...
Source: Advances in Immunology - November 10, 2019 Category: Allergy & Immunology Authors: Chen L Tags: Adv Immunol Source Type: research

Neuronal regulation of group 2 innate lymphoid cells and type 2 inflammation.
Abstract Diverse infectious, inflammatory, and environmental stimuli induce type 2 inflammation in the body. Group 2 innate lymphoid cells (ILC2s) are potent producers of type 2 cytokines and play important roles in promoting type 2 inflammation. In addition to alarmins and other cytokines which are known to regulate ILC2 responses, emerging studies identified the regulation of ILC2s by the nervous system through neurotransmitter and neuropeptides. In this review, we highlight recent advances in the regulation of ILC2s and type 2 inflammation by the nervous system. PMID: 31607366 [PubMed - in process] (Source...
Source: Advances in Immunology - October 16, 2019 Category: Allergy & Immunology Authors: Moriyama S, Artis D Tags: Adv Immunol Source Type: research

Antibody responses to the HIV-1 envelope high mannose patch.
Abstract Neutralizing antibodies against human immunodeficiency virus subtype 1 (HIV-1) bind to its envelope glycoprotein (Env). Half of the molecular mass of Env is carbohydrate making it one of the most heavily glycosylated proteins known in nature. HIV-1 Env glycans are derived from the host and present a formidable challenge for host anti-glycan antibody induction. Anti-glycan antibody induction is challenging because anti-HIV-1 glycan antibodies should recognize Env antigen while not acquiring autoreactivity. Thus, the glycan network on HIV-1 Env is referred to as the glycan shield. Despite the challenges pre...
Source: Advances in Immunology - October 16, 2019 Category: Allergy & Immunology Authors: Daniels CN, Saunders KO Tags: Adv Immunol Source Type: research

Origin and function of synovial macrophage subsets during inflammatory joint disease.
l;nke G Abstract Mononuclear phagocytes, including monocytes and macrophages, are a central component of the host's innate immune system designated to protect against invading pathogens. However, these cells do not only interact with various parts of the innate and adaptive immune system, but also fulfill indispensable duties during the control of tissue homeostasis and organ function. Moreover, macrophages are crucially involved in tissue remodeling and repair in response to damage. Simultaneously, mononuclear phagocytes might also contribute to the pathogenesis of various inflammatory and autoimmune diseases. In...
Source: Advances in Immunology - October 16, 2019 Category: Allergy & Immunology Authors: Culemann S, Grüneboom A, Krönke G Tags: Adv Immunol Source Type: research

Models of dendritic cell development correlate ontogeny with function.
Abstract Rapid advances have been made to uncover the mechanisms that regulate dendritic cell (DC) development, and in turn, how models of development can be employed to define dendritic cell function. Models of DC development have been used to define the unique functions of DC subsets during immune responses to distinct pathogens. More recently, models of DC function have expanded to include their homeostatic and inflammatory physiology, modes of communication with various innate and adaptive immune lineages, and specialized functions across different lymphoid organs. New models of DC development call for revisio...
Source: Advances in Immunology - October 16, 2019 Category: Allergy & Immunology Authors: Anderson DA, Murphy KM Tags: Adv Immunol Source Type: research

The airway epithelium in asthma.
Abstract Asthma is a genetically and phenotypically complex disease that has a major impact on global health. Signs and symptoms of asthma are caused by the obstruction of airflow through the airways. The epithelium that lines the airways plays a major role in maintaining airway patency and in host defense. The epithelium initiates responses to inhaled or aspirated substances, including allergens, viruses, and bacteria, and epithelial-derived cytokines are important in the recruitment and activation of immune cells in the airway. Changes in the structure and function of the airway epithelium are a prominent featur...
Source: Advances in Immunology - July 14, 2019 Category: Allergy & Immunology Authors: Bonser LR, Erle DJ Tags: Adv Immunol Source Type: research

Deconstructing the sex bias in allergy and autoimmunity: From sex hormones and beyond.
ry JC Abstract Men and women differ in their susceptibility to develop autoimmunity and allergy but also in their capacity to cope with infections. Mechanisms responsible for this sexual dimorphism are still poorly documented and probably multifactorial. This review discusses the recent development in our understanding of the cell-intrinsic actions of biological factors linked to sex, sex hormones and sex chromosome complement, on immune cells, which may account for the sex differences in the enhanced susceptibility of women to develop immunological disorders, such as allergic asthma or systemic lupus erythematosu...
Source: Advances in Immunology - July 14, 2019 Category: Allergy & Immunology Authors: Laffont S, Guéry JC Tags: Adv Immunol Source Type: research

Roles of cysteinyl leukotrienes and their receptors in immune cell-related functions.
Abstract The cysteinyl leukotrienes (cys-LTs), leukotriene C4, (LTC4), LTD4, and LTE4, are lipid mediators of inflammation. LTC4 is the only intracellularly synthesized cys-LT through the 5-lipoxygenase and LTC4 synthase pathway and after transport is metabolized to LTD4 and LTE4 by specific extracellular peptidases. Each cys-LT has a preferred functional receptor in vivo; LTD4 to the type 1 cys-LT receptor (CysLT1R), LTC4 to CysLT2R, and LTE4 to CysLT3R (OXGR1 or GPR99). Recent studies in mouse models revealed that there are multiple regulatory mechanisms for these receptor functions and each receptor plays a dis...
Source: Advances in Immunology - July 14, 2019 Category: Allergy & Immunology Authors: Kanaoka Y, Austen KF Tags: Adv Immunol Source Type: research

Airway mycosis in allergic airway disease.
Abstract The allergic airway diseases, including chronic rhinosinusitis (CRS), asthma, allergic bronchopulmonary mycosis (ABPM) and many others, comprise a heterogeneous collection of inflammatory disorders affecting the upper and lower airways and lung parenchyma that represent the most common chronic diseases of humanity. In addition to their shared tissue tropism, the allergic airway diseases are characterized by a distinct pattern of inflammation involving the accumulation of eosinophils, type 2 macrophages, innate lymphoid cells type 2 (ILC2), IgE-secreting B cells, and T helper type 2 (Th2) cells in airway t...
Source: Advances in Immunology - July 14, 2019 Category: Allergy & Immunology Authors: Li E, Knight JM, Wu Y, Luong A, Rodriguez A, Kheradmand F, Corry DB Tags: Adv Immunol Source Type: research

Multilayer regulation of CD4 T cell subset differentiation in the era of single cell genomics.
Abstract CD4 T cells are major immune cell types that mediate effector responses appropriate for diverse incoming threats. These cells have been categorized into different subsets based on how they are induced, expression of specific master transcription factors, and the resulting effector cell phenotypes as defined by expression of signature cytokines. However, recent studies assessing the expression of gene modules in single CD4 T cells, rather than expression of one or a few signature genes, have provided a more complex picture in which the canonical model does not fit as cleanly as proposed. Here, we review th...
Source: Advances in Immunology - March 26, 2019 Category: Allergy & Immunology Authors: Sungnak W, Wang C, Kuchroo VK Tags: Adv Immunol Source Type: research

Signaling control of antibody isotype switching.
Abstract Class switch recombination (CSR) generates isotype-switched antibodies with distinct effector functions essential for mediating effective humoral immunity. CSR is catalyzed by activation-induced deaminase (AID) that initiates DNA lesions in the evolutionarily conserved switch (S) regions at the immunoglobulin heavy chain (Igh) locus. AID-initiated DNA lesions are subsequently converted into DNA double stranded breaks (DSBs) in the S regions of Igh locus, repaired by non-homologous end-joining to effect CSR in mammalian B lymphocytes. While molecular mechanisms of CSR are well characterized, it remains les...
Source: Advances in Immunology - March 26, 2019 Category: Allergy & Immunology Authors: Chen Z, Wang JH Tags: Adv Immunol Source Type: research

Transcription factories in Ig κ allelic choice and diversity.
Transcription factories in Igκ allelic choice and diversity. Adv Immunol. 2019;141:33-49 Authors: Karki S, Banerjee S, Mclean K, Dinner A, Clark MR Abstract The vertebrate immune system is tasked with the challenge of responding to any pathogen the organism might encounter, and retaining memory of that pathogen in case of future infection. Recognition and memory of pathogens are encoded within the adaptive immune system and production of T and B lymphocytes with diverse antigen receptor repertoires. In B lymphocytes, diversity is generated by sequential recombination between Variable (V), Divers...
Source: Advances in Immunology - March 26, 2019 Category: Allergy & Immunology Authors: Karki S, Banerjee S, Mclean K, Dinner A, Clark MR Tags: Adv Immunol Source Type: research

Cis- and trans-factors affecting AID targeting and mutagenic outcomes in antibody diversification.
Abstract Antigen receptor diversification is a hallmark of adaptive immunity which allows specificity of the receptor to particular antigen. B cell receptor (BCR) or its secreted form, antibody, is diversified through antigen-independent and antigen-dependent mechanisms. During B cell development in bone marrow, BCR is diversified via V(D)J recombination mediated by RAG endonuclease. Upon stimulation by antigen, B cell undergo somatic hypermutation (SHM) to allow affinity maturation and class switch recombination (CSR) to change the effector function of the antibody. Both SHM and CSR are initiated by activation-in...
Source: Advances in Immunology - March 26, 2019 Category: Allergy & Immunology Authors: Yeap LS, Meng FL Tags: Adv Immunol Source Type: research

New Insights Into the Biology of CD8 Regulatory T Cells.
Abstract Regulatory T cells are central mediators of immune regulation and play an essential role in the maintenance of immune homeostasis in the steady state and under pathophysiological conditions. Disruption of CD8 Treg-dependent recognition of Qa-1-restricted self-antigens can result in dysregulated immune responses, tissue damage, autoimmune disease and cancer. Recent progress in studies on regulatory T cells of the CD8 lineage has provided new biological insight into this specialized regulatory T cell subpopulation. Identification of the Helios transcription factor as an essential control element for the dif...
Source: Advances in Immunology - October 29, 2018 Category: Allergy & Immunology Authors: Nakagawa H, Wang L, Cantor H, Kim HJ Tags: Adv Immunol Source Type: research

Tumor Necrosis Factor Receptor Superfamily in T Cell Priming and Effector Function.
Abstract The tumor necrosis factor receptor superfamily (TNFRSF) and their ligands mediate lymphoid tissue development and homeostasis in addition to key aspects of innate and adaptive immune responses. T cells of the adaptive immune system express a number of TNFRSF members that are used to receive signals at different instructive stages and produce several tumor necrosis factor superfamily (TNFSF) members as effector molecules. There is also one example of a TNFRSF member serving as a ligand for negative regulatory checkpoint receptors. In most cases, the ligands in afferent and efferent phases are membrane prot...
Source: Advances in Immunology - October 29, 2018 Category: Allergy & Immunology Authors: Muller J, Baeyens A, Dustin ML Tags: Adv Immunol Source Type: research

The Fly Way of Antiviral Resistance and Disease Tolerance.
Abstract Like humans, insects face the threat of viral infection. Despite having repercussions on human health and disease, knowledge gaps exist for how insects cope with viral pathogens. Drosophila melanogaster serves as an ideal insect model due to its genetic tractability. When encountering a pathogen, two major approaches to fight disease are resistance strategies and tolerance strategies. Disease resistance strategies promote the health of the infected host by reducing pathogen load. Multiple disease resistance mechanisms have been identified in Drosophila: RNA interference, Jak/STAT signaling, Toll signaling...
Source: Advances in Immunology - October 29, 2018 Category: Allergy & Immunology Authors: Chow J, Kagan JC Tags: Adv Immunol Source Type: research

The Microglial Response to Neurodegenerative Disease.
Abstract Microglia are a subset of tissue macrophages that constitute the major immune cell type of the central nervous system. These cells have long been known to change their morphology and functions in response to various neurological insults. Recently, a plethora of unbiased transcriptomics studies have revealed that across a broad spectrum of neurodegeneration-like disease models, microglia adopt a similar activation signature and perform similar functions. Despite these commonalities in response, the role of microglia has been described as both positive and negative in different murine disease models. In hum...
Source: Advances in Immunology - September 28, 2018 Category: Allergy & Immunology Authors: Song WM, Colonna M Tags: Adv Immunol Source Type: research

The First B-Cell Tolerance Checkpoint in Mice and Humans: Control by AID.
Abstract Activation-induced cytidine deaminase (AID) expression in the germinal center response drives the immunoglobulin class-switch recombination and V(D)J hypermutation necessary for efficacious, high-affinity antibody responses. That AID is expressed in developing lymphocytes is less well known, but represents an evolutionarily conserved pattern of lymphocyte development that is represented in all vertebrate species. Here we review the role of early, developmentally regulated AID expression in mice and humans and its role in establishing the first B-cell tolerance checkpoint. This newly recognized component o...
Source: Advances in Immunology - September 28, 2018 Category: Allergy & Immunology Authors: Kuraoka M, Meffre E, Kelsoe G Tags: Adv Immunol Source Type: research

RAG Chromatin Scanning During V(D)J Recombination and Chromatin Loop Extrusion are Related Processes.
Abstract An effective adaptive immune system depends on the ability of developing B and T cells to generate diverse immunoglobulin (Ig) and T cell receptor repertoires, respectively. Such diversity is achieved through a programmed somatic recombination process whereby germline V, D, and J segments of antigen receptor loci are assembled to form the variable region V(D)J exons of Ig and TCRs. Studies of this process, termed V(D)J recombination, have provided key insights into our understanding of a variety of general gene regulatory and DNA repair processes over the last several decades. V(D)J recombination is initi...
Source: Advances in Immunology - September 28, 2018 Category: Allergy & Immunology Authors: Lin SG, Ba Z, Alt FW, Zhang Y Tags: Adv Immunol Source Type: research

Eosinophil Development, Disease Involvement, and Therapeutic Suppression.
Abstract Human eosinophils have characteristic morphologic features, including a bilobed nucleus and cytoplasmic granules filled with cytotoxic and immunoregulatory proteins that are packaged in a specific manner. Eosinophil production in the bone marrow is exquisitely regulated by timely expression of a repertoire of transcription factors that work together via collaborative and hierarchical interactions to direct eosinophil development. In addition, proper granule formation, which occurs in a spatially organized manner, is an intrinsic checkpoint that must be passed for proper eosinophil production to occur. In ...
Source: Advances in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: Fulkerson PC, Rothenberg ME Tags: Adv Immunol Source Type: research

Molecular Aspects of Allergens and Allergy.
Abstract Immunoglobulin E (IgE)-associated allergy is the most common immune disorder. More than 30% of the population suffer from symptoms of allergy which are often severe, disabling, and life threatening such as asthma and anaphylaxis. Population-based birth cohort studies show that up to 60% of the world population exhibit IgE sensitization to allergens, of which most are protein antigens. Thirty years ago the first allergen-encoding cDNAs have been isolated. In the meantime, the structures of most of the allergens relevant for disease in humans have been solved. Here we provide an update regarding what has be...
Source: Advances in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: Valenta R, Karaulov A, Niederberger V, Gattinger P, van Hage M, Flicker S, Linhart B, Campana R, Focke-Tejkl M, Curin M, Eckl-Dorna J, Lupinek C, Resch-Marat Y, Vrtala S, Mittermann I, Garib V, Khaitov M, Valent P, Pickl WF Tags: Adv Immunol Source Type: research

Unexpected Roles for Intracellular Complement in the Regulation of Th1 Responses.
Abstract The complement system is generally recognized as an evolutionarily ancient and critical part of innate immunity required for the removal of pathogens that have breached the protective host barriers. It was originally defined as a liver-derived serum surveillance system that induces the opsonization and killing of invading microbes and amplifies the general inflammatory reactions. However, studies spanning the last four decades have established complement also as a vital bridge between innate and adaptive immunity. Furthermore, recent work on complement, and in particular its impact on human T helper 1 (Th...
Source: Advances in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: West EE, Afzali B, Kemper C Tags: Adv Immunol Source Type: research

Chemokines: Critical Regulators of Memory T Cell Development, Maintenance, and Function.
Abstract Memory T cells are central to orchestrating antigen-specific recall responses in vivo. Compared to naïve T cells, memory T cells respond more quickly to cognate peptide:MHC with a shorter lag time for entering the cell cycle and exerting effector functions. However, it is now well established that this enhanced responsiveness is not the only mechanism whereby memory T cells are better equipped than naïve T cells to rapidly and robustly induce inflammation. In contrast to naïve T cells, memory T cells are composed of distinct subsets with unique trafficking patterns and localizations. Tissue...
Source: Advances in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: Rahimi RA, Luster AD Tags: Adv Immunol Source Type: research

Molecular Classification of Primary Immunodeficiencies of T Lymphocytes.
Abstract Proper regulation of the immune system is required for protection against pathogens and preventing autoimmune disorders. Inborn errors of the immune system due to inherited or de novo germline mutations can lead to the loss of protective immunity, aberrant immune homeostasis, and the development of autoimmune disease, or combinations of these. Forward genetic screens involving clinical material from patients with primary immunodeficiencies (PIDs) can vary in severity from life-threatening disease affecting multiple cell types and organs to relatively mild disease with susceptibility to a limited range of ...
Source: Advances in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: Comrie WA, Lenardo MJ Tags: Adv Immunol Source Type: research

Single-Cell Resolution of T Cell Immune Responses.
Abstract Single antigen-specific B or T lymphocytes are the smallest functional units, into which an adaptive immune response can be dissected. Today, novel high-throughput technologies are providing researches with increasingly complex information on the diverse phenotypic signatures of individual lymphocytes. With a focus on T cells, we summarize here, how computational approaches are becoming increasingly important to identify the relevant developmental boundaries and connections between these high-dimensional lymphocyte states. We then describe how these insights may be further expanded by novel experimental a...
Source: Advances in Immunology - February 21, 2018 Category: Allergy & Immunology Authors: Buchholz VR, Flossdorf M Tags: Adv Immunol Source Type: research

The Unusual Genetics and Biochemistry of Bovine Immunoglobulins.
Abstract Antibodies are the key circulating molecules that have evolved to fight infection by the adaptive immune system of vertebrates. Typical antibodies of most species contain six complementarity-determining regions (CDRs), where the third CDR of the heavy chain (CDR H3) has the greatest diversity and often makes the most significant contact with antigen. Generally, the process of V(D)J recombination produces a vast repertoire of antibodies; multiple V, D, and J gene segments recombine with additional junctional diversity at the V-D and D-J joints, and additional combinatorial possibilities occur through heavy...
Source: Advances in Immunology - February 21, 2018 Category: Allergy & Immunology Authors: Stanfield RL, Haakenson J, Deiss TC, Criscitiello MF, Wilson IA, Smider VV Tags: Adv Immunol Source Type: research