Role of Dsg1- and Dsg3-Mediated Signaling in Pemphigus Autoantibody-Induced Loss of Keratinocyte Cohesion
2 ABSTRACT 3 Pemphigus is an autoimmune dermatosis in which mucocutaneous blisters are induced primarily 4 by autoantibodies against Desmoglein (Dsg) 1 and 3. Pemphigus vulgaris (PV) usually is 5 associated with autoantibodies against Dsg3 whereas pemphigus foliaceus (PF) patients present 6 autoantibodies against Dsg1. Several signaling pathways were proposed to cause loss of 7 keratinocyte adhesion. However, relevance of different signaling pathways and role of Dsg1 8 and 3 to trigger signaling are not fully understood. Here, we show that Ca2+ chelation reduced 9 PV-IgG- and PF-IgG-mediated loss of HaCaT keratinocy...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

Direct Inhibition of IRF-Dependent Transcriptional Regulatory Mechanisms Associated With Disease
Interferon regulatory factors (IRFs) are a family of homologous proteins that regulate the transcription of interferons (IFNs) and interferon-induced gene expression. As such they are important modulating proteins in the Toll-like receptor (TLR) and interferon signaling pathways, which are vital elements of the innate immune system. IRFs have a multi-domain structure, with the N-terminal part acting as a DNA binding domain (DBD) that recognizes a DNA-binding motif similar to the IFN-stimulated response element (ISRE). The C-terminal part contains the IRF-association domain (IAD), with which they can self-associate, bind to...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

Ontogeny of Synovial Macrophages and the Roles of Synovial Macrophages From Different Origins in Arthritis
The objective of this study was designed to investigate the ontogeny of SM and to evaluate the role of SM from different origins in arthritis. SM was isolated from Cxcr1-EGFP mice and C57BL/6 mice by a strigent sorting strategy. Flow cytometry, immunostaining and bone marrow chimera model were used to identify different origins of SM. The comparison of cellular features of SM from different origins were evaluated by the total cell number, in situ proliferation, phagocytosis and expressions of pro-inflammatory and anti-inflammatory genes. In addition, collagen-induced arthritis (CIA) mice and rheumatoid arthritis (RA) patie...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

The Role of Monocytes and Macrophages in Autoimmune Diseases: A Comprehensive Review
Monocytes (Mo) and macrophages (Mφ) are key components of the innate immune system and are involved in regulation of the initiation, development and resolution of many inflammatory disorders. In addition, these cells also play important immunoregulatory and tissue-repairing roles to decrease immune reactions and promote tissue regeneration. Several lines of evidence have suggested a causal link between the presence or activation of these cells and the development of autoimmune diseases. In addition, Mo or Mφ infiltration in diseased tissues is a hallmark of several autoimmune diseases. However, the detailed contrib...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

CAR T Cells Targeting the Tumor MUC1 Glycoprotein Reduce Triple-Negative Breast Cancer Growth
Antibody-derived chimeric antigen receptor (CAR) T cell therapy has achieved gratifying breakthrough in hematologic malignancies but has shown limited success in solid tumor immunotherapy. Monoclonal antibody, TAB004, specifically recognizes the aberrantly glycosylated tumor form of MUC1 (tMUC1) in all subtypes of breast cancer including 95% of triple-negative breast cancer (TNBC) while sparing recognition of normal tissue MUC1. We transduced human T cells with MUC28z, a chimeric antigen receptor comprising of the scFv of TAB004 coupled to CD28 and CD3ζ. MUC28z was well expressed on the surface of engineered activated...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

The Epitope-Specific Anti-human CD4 Antibody MAX.16H5 and Its Role in Immune Tolerance
T cell modulation in the clinical background of autoimmune diseases or allogeneic cell and organ transplantations with concurrent preservation of their natural immunological functions (e.g. pathogen defense) is the major obstacle in immunology. An anti human CD4 antibody (MAX.16H5) was applied intravenously in clinical trials for the treatment of autoimmune diseases (e.g. rheumatoid arthritis) and acute late-onset rejection after transplantation of a renal allograft. The response rates were remarkable and no critical allergic problems or side effects were obtained. During the treatment of autoimmune diseases with the murin...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

Identification of LPS-Activated Endothelial Subpopulations With Distinct Inflammatory Phenotypes and Regulatory Signaling Mechanisms
Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Endothelial cells (EC) are actively involved in sepsis-associated (micro)vascular disturbances and subsequent organ dysfunction. Lipopolysaccharide (LPS), a Gram-negative bacterial product, can activate EC leading to the expression of pro-inflammatory molecules. This process is molecularly regulated by specific receptors and distinct, yet poorly understood intracellular signaling pathways. LPS-induced expression of endothelial adhesion molecules E-selectin and VCAM-1 in mice was previously shown to be organ- and microvascular-specif...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS –) vs. Alternatively Activated Macrophages
Macrophages are found in tissues, body cavities, and mucosal surfaces. Most tissue macrophages are seeded in the early embryo before definitive hematopoiesis is established. Others are derived from blood monocytes. The macrophage lineage diversification and plasticity are key aspects of their functionality. Macrophages can also be generated from monocytes in vitro and undergo classical (LPS+IFN-γ) or alternative (IL-4) activation. In vivo, macrophages with different polarization and different activation markers coexist in tissues. Certain mouse strains preferentially promote T-helper-1 (Th1) responses and other Th2 r...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

A Hepatitis C Virus DNA Vaccine Encoding a Secreted, Oligomerized Form of Envelope Proteins Is Highly Immunogenic and Elicits Neutralizing Antibodies in Vaccinated Mice
This report provides the first evidence that IMX313P can be used as an adjuvant for E1/E2-based DNA vaccines and represents a translatable approach for the development of a HCV DNA vaccine. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

Systems Immunology Characterization of Novel Vaccine Formulations for Mycoplasma hyopneumoniae Bacterins
We characterized five different vaccine candidates and a commercial vaccine in terms of safety, immunogenicity and using a system vaccinology approach, with the aim to select novel vaccine candidates against Mycoplasma hyopneumoniae. Seven groups of six M. hyopneumoniae-free piglets were primo- and booster vaccinated with the different experimental bacterin formulations, the commercial vaccine Hyogen® as a positive control or PBS as a negative control. The experimental bacterin was formulated with cationic liposomes + c-di-AMP (Lipo_AMP), cationic liposomes + Toll-like receptor (TLR) 2/1, TLR7 and TLR9 ligands (TLR lig...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

Interleukin-36 in Infectious and Inflammatory Skin Diseases
Interleukin 36 (IL 36) comprises to a cytokine family consisting of four isoforms IL 36, IL 36, IL 36, and IL 36 receptor antagonist (IL 36 Ra). These IL 36 cytokines, in turn, belong to the IL 1 superfamily. The IL 36 receptor (IL 1R6) is functional as a heterodimer formed of IL-1R6 and IL 1 receptor accessory protein (IL 1RAcP). IL 36, IL 36, and IL 36 are regarded as pro-inflammatory ligands and IL 36 Ra as well as IL-38 as anti-inflammatory ligands of IL 1R6. IL-36 cytokines are mainly expressed on the barrier sites of the body e.g. bronchial, intestinal and dermal epithelium. One of their most import...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

Co- but not Sequential Infection of DCs Boosts Their HIV-Specific CTL-Stimulatory Capacity
Pathogenic bacteria and their microbial products activate dendritic cells (DCs) at mucosal surfaces during sexually transmitted infections (STIs) and therefore might also differently shape DC functions during co-infection with HIV-1. We recently illustrated that complement (C) coating of HIV-1 (HIV-C), as primarily found during the acute phase of infection before appearance of HIV-specific antibodies, by-passed SAMHD1-mediated restriction in DCs and therefore mediated an increased DC activation and antiviral capacity. To determine whether the superior antiviral effects of HIV-C-exposed DCs also apply during STIs, we develo...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

Structural Modification of the Antidepressant Mianserin Suggests That Its Anti-inflammatory Activity May Be Independent of 5-Hydroxytryptamine Receptors
Antidepressants are increasingly recognized to have anti-inflammatory properties in addition to their ability to treat major depressive disorders. To explore if engagement of 5-hydroxytryptamine (5-HT) receptors was required for the anti-inflammatory effect of the tetracyclic antidepressant mianserin, a series of structural derivatives were generated with the aim of reducing 5-HT receptor binding. Primary human peripheral blood mononuclear cells were used to screen for anti-inflammatory activity. The lead compound demonstrated a significant loss in 5-HT receptor binding, as assessed by non-selective 5-HT binding of radiola...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

Notch Signaling Regulates Immune Responses in Atherosclerosis
Atherosclerosis is a chronic autoimmune inflammatory disease that can cause coronary artery disease, stroke, peripheral artery disease, depending on which arteries are affected. At the beginning of atherosclerosis plasma lipoproteins accumulate in the sub-endothelial space. In response, monocytes migrate from the circulation through the endothelium into the intima where they differentiate into macrophages. These early events trigger a complex immune response that eventually involves many cellular subtypes of both innate and adaptive immunity. The Notch signaling pathway is an evolutionary conserved cell signaling system th...
Source: Frontiers in Immunology - May 23, 2019 Category: Allergy & Immunology Source Type: research

Disruption of Telomere Integrity and DNA Repair Machineries by KML001 Induces T Cell Senescence, Apoptosis, and Cellular Dysfunctions
T cells in chronic viral infections are featured by premature aging with accelerated telomere erosion, but the mechanisms underlying telomere attrition remain unclear. Here, we employed human CD4 T cells treated with KML001 (a telomere-targeting drug) as a model to investigate the role of telomere integrity in remodeling T cell senescence. We demonstrated that KML001 could inhibit cell proliferation, cytokine production, and promote apoptosis via disrupting telomere integrity and DNA repair machineries. Specifically, KML001-treated T cells increased dysfunctional telomere-induced foci (TIF), DNA damage marker γH2AX, ...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Adipose Tissue-Resident Immune Cells in Obesity and Type 2 Diabetes
Inflammation is an important contributor to the pathogenesis of obesity-related type 2 diabetes (T2D). Adipose tissue-resident immune cells have been observed, and the potential contribution of these cells to metabolic dysfunction has been appreciated in recent years. This review focused on adipose tissue-resident immune cells that are dysregulated in the context of obesity and T2D. We comprehensively overviewed emerging knowledge regarding the phenotypic and functional properties of these cells and local factors that control their development. We discussed their function in controlling the immune response cascade and dise...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

The CD14+HLA-DRlo/neg Monocyte: An Immunosuppressive Phenotype That Restrains Responses to Cancer Immunotherapy
Recent successes in cancer immunotherapy have been tempered by sub-optimal clinical responses in the majority of patients. The impaired anti-tumor immune responses observed in these patients are likely a consequence of immune system dysfunction contributed to by a variety of factors that include, but are not limited to, diminished antigen presentation/detection, leukopenia, a coordinated network of immunosuppressive cell surface proteins, cytokines and cellular mediators. Monocytes that have diminished or no HLA-DR expression, called CD14+HLA-DRlo/neg monocytes, have emerged as important mediators of tumor-induced immunosu...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

The BTLA –HVEM–CD5 Immunoregulatory Axis–An Instructive Mechanism Governing pTreg Cell Differentiation
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Current Concepts on 6-sulfo LacNAc Expressing Monocytes (slanMo)
The human mononuclear phagocyte system consists of dendritic cells (DCs), monocytes and macrophages having different functions in bridging innate and adaptive immunity. Among the heterogeneous population of monocytes the cell surface marker slan (6-sulfo LacNAc) identifies a specific subset of human CD14- CD16+ non-classical monocytes, called slan+ monocytes (slanMo). In this review we discuss the identity and functions of slanMo, their contributions to immune surveillance by proinflammatory cytokine production, and cross talk with T cells and NK cells. We also consider the role of slanMo in the regulation of chronic infla...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Interferon Regulatory Factors 1 and 2 Play Different Roles in MHC II Expression Mediated by CIITA in Grass Carp, Ctenopharyngodon idella
In this study, the characterization of CIITA was identified and its functional domains were analyzed in grass carp. The absence of GAS and E-box in the promoter region of grass carp CIITA, might imply that the cooperative interaction between STAT1 and USF1 to active the CIITA expression, found in mammals, is not present in bony fish. After the transfection of IFN-γ or IFN-γ rel, only IFN-γ could induce MHC II expression mediated by CIITA. Moreover, interferon regulatory factor (IRF) 2, which cooperates with IRF1 to active the CIITA promoter IV expression in mammals, played an antagonistic role to IRF1 in ...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Simultaneous and Positively Correlated NET Formation and Autophagy in Besnoitia besnoiti Tachyzoite-Exposed Bovine Polymorphonuclear Neutrophils
Given that B. besnoiti tachyzoites infect host endothelial cells of vessels in vivo, they become potential targets for professional phagocytes [e. g. polymorphonuclear neutrophils (PMN)] when in search for adequate host cells or in case of host cell lysis. It was recently reported that B. besnoiti-tachyzoites can efficiently be trapped by neutrophil extracellular traps (NETs) released by bovine PMN. So far, the potential role of autophagy in parasite-triggered ET formation is unclear. Thus, we here analyzed autophagosome formation and activation of AMP-activated protein kinase α (AMPKα) in potentially ET-formin...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Monkeying Around: Using Non-human Primate Models to Study NK Cell Biology in HIV Infections
Natural killer (NK) cells are the major innate effectors primed to eliminate virus-infected and tumor or neoplastic cells. Recent studies also suggest nuances in phenotypic and functional characteristics among NK cell subsets may further permit execution of regulatory and adaptive roles. Animal models, particularly non-human primate (NHP) models, are critical for characterizing NK cell biology in disease and under homeostatic conditions. In HIV infection, NK cells mediate multiple antiviral functions via upregulation of activating receptors, inflammatory cytokine secretion, antibody dependent cell cytotoxicity through anti...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Long Chain Polyunsaturated Fatty Acids (LCPUFAs) in the Prevention of Food Allergy
N-3 long chain polyunsaturated fatty acids (LCPUFAs) are considered to possess protective properties for human health by impacting on immunological reactions. An ‘inflammation-suppressive’ effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as (food) allergy. LCPUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy in pre-clinical models. In this review, we explore the anti-allergic properties of LCPUFAs by ...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Combinatorial Approaches With Checkpoint Inhibitors to Enhance Anti-tumor Immunity
Treatment of tumor patients has been recently revolutionized by the application of various immunotherapeutics. However, the response rates are still limited ranging between approximately 20 and 40% suggesting that combinations of immunotherapy with conventional therapies, such as chemotherapy, radiotherapy as well as epigenetic modulators, targeted therapies using small molecules as well as other (immuno)therapeutics, might be an option to increase systemic anti-tumor immunity. It has been suggested that these non-immune based therapies in combination with immunotherapies could reprogram the immune suppressive tumor microm...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Excessive miR-152-3p Results in Increased BAFF Expression in SLE B-Cells by Inhibiting the KLF5 Expression
This study aimed to uncover the mechanisms that regulate the BAFF expression in SLE B-cells. The results demonstrated that the expression of miR-152-3p was significantly increased in SLE B-cells compared with normal controls. This study confirmed that Kruppel-like factor 5 (KLF5) was a direct target of miR-152-3p, and it could bind to the promoter region of BAFF and inhibit its expression in B-cells. The upregulation of miRNA-152-3p expression decreased the KLF5 expression and increased the BAFF expression in SLE B-cells. Knockdown of miR-152-3p expression inhibited the self-reactivity of SLE B-cells, thereby reducing the ...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Complement System Inhibition Modulates the Pro-Inflammatory Effects of a Snake Venom Metalloproteinase
Envenomation by Bothrops snakes causes prominent local effects, including pain, oedema, local bleeding, blistering and necrosis, and systemic manifestations, such as haemorrhage, hypotension, shock and acute renal failure. These snake venoms are able to activate the complement system and induce the generation of anaphylatoxins, whose mechanisms include the direct cleavage of complement components by snake venom metalloproteinases and serine proteinases present in the venoms. A metalloproteinase able to activate the three complement pathways and generate active anaphylatoxins, named C-SVMP, was purified from the venom of Bo...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

β-Glycosphingolipids as Mediators of Both Inflammation and Immune Tolerance: A Manifestation of Randomness in Biological Systems
Plasticity in biological systems is attributed to the combination of multiple parameters which determine function. These include genotypic, phenotypic, and environmental factors. While biological processes can be viewed as ordered and sequential, biological randomness was suggested to underline part of them. The present review looks into the concept of randomness in biological systems by exploring the glycosphingolipids-NKT cells example. NKT cells are a unique subset of regulatory lymphocytes which play a role in both inflammation and tolerance. Glycosphingolipids promote an immune balance by changing different arms of th...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Microbicidal Phagocytosis of Nucleus Pulposus Cells Against Staphylococcus aureus via the TLR2/MAPKs Signaling Pathway
Intervertebral disc (IVD) is an immune-privilege organ that lacks immunocytes, such as macrophages or neutrophils; therefore, it is unclear how IVD immunological defense against bacterial infection occurs. Here, we demonstrated that nucleus pulposus cells (NPCs), the vital machinery for maintaining the homeostasis of IVD, exerted microbicidal activity against Staphylococcus aureus via induction of phagolysosome formation. Moreover, we found that the Toll-like receptor 2 (TLR2)/mitogen-activated protein kinases (MAPKs) signaling pathway is critical for bacterial phagocytosis and phagolysosome formation of NPCs. These findin...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment
The immune system and cancer have a complex relationship with the immune system playing a dual role in tumor development. The effector cells of the immune system can recognize and kill malignant cells while immune system-mediated inflammation can also promote tumor growth and regulatory cells suppress the anti-tumor responses. In the center of all anti-tumor responses is the ability of the immune cells to migrate to the tumor site and to interact with each other and with the malignant cells. Cell adhesion molecules including receptors of the immunoglobulin superfamily and integrins are of crucial importance in mediating th...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Fish Red Blood Cells Modulate Immune Genes in Response to Bacterial Inclusion Bodies Made of TNF α and a G-VHSV Fragment
Fish Red-Blood Cells (RBCs) are nucleated cells that can modulate the expression of different sets of genes in response to stimuli, playing an active role in the homeostasis of the fish immune system. Nowadays, vaccination is one of the main ways to control and prevent viral diseases in aquaculture and the development of novel vaccination approaches is a focal point in fish vaccinology. One of the strategies that has recently emerged is the use of nanostructured recombinant proteins. Nanostructured cytokines have already been shown to immunostimulate and protect fish against bacterial infections. To explore the role of RBC...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Anti-inflammatory Trained Immunity Mediated by Helminth Products Attenuates the Induction of T Cell-Mediated Autoimmune Disease
Recent studies have suggested that the innate immune system can display characteristics of immunological memory and this has been called ‘innate immune memory’ or ‘trained immunity’. Certain fungal products have been shown to induce epigenetic imprinting on monocytes/macrophages that results in heightened inflammatory responses to subsequent stimulus. Here we report that innate immune cells can be trained to be more anti-inflammatory following exposure to products of a helminth pathogen. Macrophages trained in vitro with Fasciola hepatica total extract (FHTE) had enhanced IL-10 and IL-1RA, but reduc...
Source: Frontiers in Immunology - May 21, 2019 Category: Allergy & Immunology Source Type: research

Molecular Characterization of Monocyte Subsets Reveals Specific and Distinctive Molecular Signatures Associated With Cardiovascular Disease in Rheumatoid Arthritis
Conclusions: Our overall data suggest that the generation of inflammatory monocytes is associated to the autoimmune/inflammatory response that mediates RA. These monocyte subsets, -which display specific and distinctive molecular signatures- might promote endothelial dysfunction and in turn, the progression of atherosclerosis through a finely regulated process driving CVD development in RA. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - May 21, 2019 Category: Allergy & Immunology Source Type: research

Autologous Hematopoietic Stem Cells Are a Preferred Source to Generate Dendritic Cells for Immunotherapy in Multiple Myeloma Patients
This study has implications in increasing the efficacy of cancer immunotherapy in MM. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - May 21, 2019 Category: Allergy & Immunology Source Type: research

Cell of Origin and Genetic Alterations in the Pathogenesis of Multiple Myeloma
B cell activation and differentiation yields plasma cells with high affinity antibodies to a given antigen in a time-frame that allows for host protection. Although the end product is most commonly humoral immunity, the rapid proliferation and somatic mutation of the B cell receptor also results in oncogenic mutations that cause B cell malignancies including plasma cell neoplasms such as multiple myeloma. Myeloma is the second most common hematological malignancy and results in over 100,000 deaths per year worldwide. The genetic alterations that occur in the germinal center, however, are not sufficient to cause myeloma, bu...
Source: Frontiers in Immunology - May 21, 2019 Category: Allergy & Immunology Source Type: research

Association of LRP1B Mutation With Tumor Mutation Burden and Outcomes in Melanoma and Non-small Cell Lung Cancer Patients Treated With Immune Check-Point Blockades
Conclusion: Our studies suggested sequencing even a single, frequently mutated gene may provide insight into genome-wide mutational burden, and may serve as a biomarker to predict immune response. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - May 21, 2019 Category: Allergy & Immunology Source Type: research

The Role of Membrane Bound Complement Regulatory Proteins in Tumor Development and Cancer Immunotherapy
It has long been understood that the control and surveillance of tumors within the body involves an intricate dance between the adaptive and innate immune systems. At the center of the interplay between the adaptive and innate immune response sits the complement system- an evolutionarily ancient response that aids in the destruction of microorganisms and damaged cells, including cancer cells. Membrane-bound complement regulatory proteins, (mCRPs) such as CD46, CD55 and CD59, are expressed throughout the body in order to prevent over-activation of the complement system. These mCRPs act as a double-edged sword however, as th...
Source: Frontiers in Immunology - May 21, 2019 Category: Allergy & Immunology Source Type: research

Mechanistic Characterization of RASGRP1 Variants Identifies an hnRNP-K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility
Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic component. We recently identified a novel SLE susceptibility locus near RASGRP1, which governs the ERK/MAPK kinase cascade and B-/T-cell differentiation and development. However, precise causal RASGRP1 functional variant(s) and their mechanisms of action in SLE pathogenesis remain undefined. Our goal was to fine-map this locus, prioritize genetic variants according to likely functionality, experimentally validate the contribution of three SNPs to SLE risk, and experimentally determine their biochemical mechanisms of action. We performed a met...
Source: Frontiers in Immunology - May 20, 2019 Category: Allergy & Immunology Source Type: research

ATP Triggers Human Th9 Cell Differentiation via Nitric Oxide-Mediated mTOR-HIF1 α Pathway
Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial effector function in inducing allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumour immune responses. Although the cytokines that lead to the differentiation of human Th9 cells have been identified, other factors that support the differentiation of Th9 cells have not been identified yet. Here we show that the extracellular ATP (eATP) induces the differentiation of Th9 cells. We further show that eATP induces the production of nitric oxide (NO), which creates a feed forward loop in the differentiation of human Th9 cells, as...
Source: Frontiers in Immunology - May 20, 2019 Category: Allergy & Immunology Source Type: research

Dysregulation of Intestinal Epithelial Cell RIPK Pathways Promotes Chronic Inflammation in the IBD Gut
This article will review these dysregulated RIPK pathways in IEC and their role in promoting chronic inflammation. It will also highlight future research directions and therapeutic approaches involving RIPKs in IBD. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - May 20, 2019 Category: Allergy & Immunology Source Type: research

Vascular Smooth Muscle Cells Contribute to Atherosclerosis Immunity
Vascular smooth muscle cells (VSMCs) constitute the major cells in the media layer of arteries, and are critical to maintain the integrity of the arterial wall. They participate in arterial wall remodeling, and play important roles in atherosclerosis throughout all stages of the disease. Studies demonstrate that VSMCs can adopt numerous phenotypes depending on inputs from endothelial cells (ECs) of the intima, resident cells of the adventitia, circulating immune cells, hormones, and plasma lipoproteins. This plasticity allows them to perform multiple tasks in physiology and disease. In this minireview, we focus on a previo...
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research

Myeloid Cell and Transcriptome Signatures Associated With Inflammation Resolution in a Model of Self-Limiting Acute Brain Inflammation
Inflammation contributes to tissue repair and restoration of function after infection or injury. However, some forms of inflammation can cause tissue damage and disease, particularly if inappropriately activated, excessive, or not resolved adequately. The mechanisms that prevent excessive or chronic inflammation are therefore important to understand. This is particularly important in the central nervous system where some effects of inflammation can have particularly harmful consequences, including irreversible damage. An increasing number of neurological disorders, both acute and chronic, and their complications are associ...
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research

Effects of Neutrophil Extracellular Traps on Bovine Mammary Epithelial Cells in vitro
In this study, the cytotoxicity of NETs on BMEC was determined using LDH Cytotoxicity Assay Kit, and the viability of cells was examined by Cell Counting Kit-8. Histone-induced bovine mammary epithelial cells damage was examined by flow cytometry and immunofluorescence analysis. The activities of caspase 1, caspase 3, caspase 11 and NLRP3 was detected using Western blot and immunohistochemical analysis. The results showed that NETs and their component histones significantly increased cytotoxicity to bovine mammary epithelial cells, which suggests the critical role of NETs and their component histones in BMEC damage. In add...
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research

Influenza A Virus Infection Induces Hyperresponsiveness in Human Lung Tissue-Resident and Peripheral Blood NK Cells
NK cells in the human lung respond to influenza A virus- (IAV-) infected target cells. However, the detailed functional capacity of human lung and peripheral blood NK cells remains to be determined in IAV and other respiratory viral infections. Here, we investigated the effects of IAV infection on human lung and peripheral blood NK cells in vitro and ex vivo following clinical infection. IAV infection of lung- and peripheral blood-derived mononuclear cells in vitro induced NK cell hyperresponsiveness to K562 target cells, including increased degranulation and cytokine production particularly in the CD56brightCD16- subset o...
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research

Gastric Subserous Vaccination With Helicobacter pylori Vaccine: An Attempt to Establish Tissue-Resident CD4+ Memory T Cells and Induce Prolonged Protection
This study investigates the vaccine-induced gastric CD4+ Trm cells in a mice model, and highlights the need for designing a vaccine strategy against H. pylori by establishing the protective CD4+ Trm cells. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research

Investigation of Oligoclonal IgG Bands in Tear Fluid of Multiple Sclerosis Patients
Conclusion: Due to the limited concordance, high rate of samples with insufficient material, and the unknown origin of tear IgG we cannot recommend that tear OCB detection may replace CSF OCB detection in MS patients. The detection of unique OCB in tears might offer new insights in ophthalmological diseases. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research

Functional Phenotypic Diversity of Regulatory T Cells Remaining in Inflamed Skin
Regulatory T cells (Tregs) migrate between lymphoid and peripheral tissues for maintaining immune homeostasis. Tissue-specific function and functional heterogeneity of Tregs have been suggested, however, correlation between them and inter-tissue movement remain unknown. We used a contact hypersensitivity model of mice expressing a photoconvertible protein for tracking migratory cells. After marking cells in skin, we purified Tregs exhibiting a different migration pattern [Tregs recruiting to or remaining in the skin and emigrating from the skin to draining lymph nodes (dLNs) within half a day] and examined single-cell gene...
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research

OTUD6B-AS1 Might Be a Novel Regulator of Apoptosis in Systemic Sclerosis
Antisense long noncoding RNAs (AS lncRNAs) have increasingly been recognized as important regulators of gene expression and they have been found to play key roles in several diseases. However, very little is known about the role of AS lncRNAs in fibrotic diseases such as systemic sclerosis (SSc). Our recent screening experiments by RNA sequencing showed that ovarian tumor domain containing 6B antisense RNA1 (OTUD6B-AS1) and its sense gene OTUD6B were significantly downregulated in SSc skin biopsies. Therefore, we aimed to identify key regulators of OTUD6B-AS1 and to analyze the functional relevance of OTUD6B-AS1 in SSc. ...
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research

Fluctuating and Geographically Specific Selection Characterize Rapid Evolution of the Human KIR Region
The killer-cell immunoglobulin-like receptor (KIR) is a fast-evolving family of genes that encode receptors for natural killer (NK) cells and have crucial role in host defense. Evolution of the KIR genes was examined in the context of the human genome. Gene-content diversity and single nucleotide polymorphisms (SNP) in the KIR genes and flanking regions were compared to>660,000 genome-wide SNPs in over 800 individuals from 52 populations of the human genome diversity panel (HGDP). KIR allelic diversity was further examined using next generation sequencing in a subset of 56 individuals. We identified the SNP rs587560 loc...
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research

Circulating Levels of Interferon Regulatory Factor-5 Associates With Subgroups of Systemic Lupus Erythematosus Patients
Systemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disease, which currently lacks specific diagnostic biomarkers. The diversity within the patients obstructs clinical trials but may also reflect differences in underlying pathogenesis. Our objective was to obtain protein profiles to identify potential general biomarkers of SLE and to determine molecular subgroups within SLE for patient stratification. Plasma samples from a cross-sectional study of well-characterized SLE patients (n=379) and matched population controls (n=316) were analyzed by antibody suspension bead array targeting 281 proteins. To investi...
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research

TH1-Polarized TFH Cells Delay Naturally-Acquired Immunity to Malaria
Humoral immunity is a critical effector arm for protection against malaria but develops only slowly after repeated infections. T cell-mediated regulatory dynamics affect the development of antibody responses to Plasmodium parasites. Here, we hypothesize that T follicular helper cell (TFH) polarization generated by repeated Plasmodium asexual blood-stage infections delays the onset of protective humoral responses. IFN-γ production promotes polarization towards TFH1 and increased generation of regulatory follicular helper cells (TFR). Delineating the mechanisms that drive TH1 polarisation will provide clues for appropr...
Source: Frontiers in Immunology - May 17, 2019 Category: Allergy & Immunology Source Type: research