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Autoimmunity t cell

Yulin Chen, Jie Wu, Jiajia Wang, Wenjing Zhang, Bohui Xu, Xiaojun Xu, Li Zong
AIMS/HYPOTHESIS: The intestinal immune system is an ideal target to induce immune tolerance physiologically. However, the efficiency of oral protein antigen delivery is limited by degradation of the antigen in the gastrointestinal tract and poor uptake by antigen-presenting cells. Gut dendritic cells (DCs) are professional antigen-presenting cells that are prone to inducing antigen-specific immune tolerance. In this study, we delivered the antigen heat shock protein 65-6×P277 (H6P) directly to the gut DCs of NOD mice through oral vaccination with H6P-loaded targeting nanoparticles (NPs), and investigated the ability of this antigen to induce immune tolerance to prevent autoimmune diabetes in NOD mice...
March 15, 2018: Diabetologia
Peijuan Wang, Yan Lu, Si Chen, Yue Chen, Chunping Hu, Yawei Zuo
Autoimmune abnormality is one of the main causes of premature ovarian failure (POF). Bu Shen Huo Xue formula (BSHXF), a traditional Chinese medicine formula, has been clinically used for the treatment of patients with POF in China. Regulatory T cells (Tregs) are important in the pathogenesis of autoimmune POF. The aim of the present study was to evaluate the immunoprotective effects of BSHXF on POF and the underlying mechanisms. An experimental autoimmune POF model was induced in B6AF1 mice with zona pellucida 3 (ZP3) fragments...
April 2018: Experimental and Therapeutic Medicine
Zimu Zhang, Zhenyi Xue, Ying Liu, Hongkun Liu, Xiangdong Guo, Yan Li, Hongwei Yang, Lijuan Zhang, Yurong Da, Zhi Yao, Rongxin Zhang
Among T helper (Th) cell subsets differentiated from naive CD4+ T cells, IL-17-producing Th17 cells are closely associated with the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and the MS animal model, experimental autoimmune encephalomyelitis (EAE). The modulation of Th17 differentiation offers a potential avenue for treatment. Although a series of microRNAs (miRNAs) that modulate autoimmune disease development have been reported, further studies on miRNA roles in Th17 differentiation and MS pathogenesis are still warranted...
March 12, 2018: Brain, Behavior, and Immunity
Allison M Weis, Raymond Soto, June L Round
The commensal microbiota influences many aspects of immune system regulation, including T cells, but molecular details of how this occurs are largely unknown. Here we review our findings that the microbiota regulates Erdr1, a secreted apoptotic factor, to control T cell survival. Erdr1 is highly upregulated in CD4+ T cells from germfree mice and antibiotic treated animals, and our study shows that Erdr1 is suppressed by the microbiota via Toll-like receptor signaling and MyD88 dependent pathways. Erdr1 functions in an autocrine fashion and promotes apoptosis through the FAS/FASL pathway...
March 15, 2018: Gut Microbes
Adriano Luís Soares De Souza, Stefan Rudin, Rui Chang, Keith Mitchell, Timothy Crandall, Shuning Huang, Ji-Kyung Choi, Shinji L Okitsu, Danielle L Graham, Blake Tomkinson, Tammy Dellovade
INTRODUCTION: Antigen-specific immunotherapy could provide a targeted approach for the treatment of multiple sclerosis that removes the need for broad-acting immunomodulatory drugs. ATX-MS-1467 is a mixture of four peptides identified as the main immune-dominant disease-associated T-cell epitopes in myelin basic protein (MBP), an autoimmune target for activated autoreactive T cells in multiple sclerosis. Previous animal studies have shown that ATX-MS-1467 treatment prevented the worsening of signs of disease in experimental autoimmune encephalitis (EAE) in the humanized (DR2 × Ob1)F1 mouse in a dose-dependent fashion...
March 14, 2018: Neurology and Therapy
Jianbo Chen, Yao Zhang, Yunsheng Liang, Ming Zhao, Hai Long, Rong Xiao, Haijing Wu, Jieyue Liao, Shuaihantian Luo, Guiying Zhang, Qianjin Lu
Pemphigus vulgaris is an autoimmune blistering disease characterized by a loss of epidermal cell-cell adhesion caused by anti-desmoglein (Dsg) autoantibodies. The pathogenesis of PV remains unclear. However, abnormal frequency and function of Th2 cells are believed to contribute to PV. We investigated Nr4a2, a transcription factor, which has been found to regulate T cell differentiation, for its association with Th2 cell differentiation and functions in PV. We found significantly decreased mRNA and protein levels of Nr4a2 in CD4+ T cells from patients with PV, compared with healthy control subjects...
February 16, 2018: Oncotarget
Emma L Smith, Mark Peakman
Autoimmune and allergic diseases occur when an individual mounts an inappropriate immune response to a self-antigen or an innocuous environmental antigen. This triggers a pathogenic T-cell response resulting in damage to specific tissues and organs. In type 1 diabetes (T1D), this manifests as destruction of the insulin-secreting β cells, resulting in a life-long dependency on recombinant insulin. Modulation of the pathogenic T-cell response with antigen-specific peptide immunotherapy offers the potential to restore the immune homeostasis and prevent further tissue destruction...
2018: Frontiers in Immunology
Antonella Mancusi, Sara Piccinelli, Andrea Velardi, Antonio Pierini
FoxP3+ regulatory T cells (Tregs) are a subset of CD4+ T cells that can suppress proliferation and effector functions of T cells, B cells, NK cells, and antigen-presenting cells. Treg deficiency causes dramatic immunologic disease in both animal models and humans. As they are capable to suppress the function and the proliferation of conventional CD4+ and CD8+ T cells, Treg-based cell therapies are under evaluation for the treatment of various autoimmune diseases and are currently employed to prevent graft-versus-host disease (GvHD) in clinical trials of hematopoietic stem cell transplantation...
2018: Frontiers in Immunology
Emilia Vendelova, Diyaaeldin Ashour, Patrick Blank, Florian Erhard, Antoine-Emmanuel Saliba, Ulrich Kalinke, Manfred B Lutz
Dendritic cells (DCs) are key directors of tolerogenic and immunogenic immune responses. During the steady state, DCs maintain T cell tolerance to self-antigens by multiple mechanisms including inducing anergy, deletion, and Treg activity. All of these mechanisms help to prevent autoimmune diseases or other hyperreactivities. Different DC subsets contribute to pathogen recognition by expression of different subsets of pattern recognition receptors, including Toll-like receptors or C-type lectins. In addition to the triggering of immune responses in infected hosts, most pathogens have evolved mechanisms for evasion of targeted responses...
2018: Frontiers in Immunology
Min Yang, Li Su, Qin Tao, Chenxi Zhang, Yueyue Wu, Jun Liu
Hashimoto's Thyroiditis (HT) is a common organ-specific autoimmune disorder associated with a high incidence, and insulin resistance is highly related to autoimmune. Here, we examined the insulin sensitivity in HT patients and found decreased insulin sensitivity occurred in HT patients. To explore the relationship between impaired insulin sensitivity and immune status, we established HT model mice which showed similar pathological features and immune features to HT patients. In HT model mice, reinfusion of regulatory T cells (Tregs) from peripheral blood of normal mice could improve insulin sensitivity and decrease the inflammation...
2018: Frontiers in Physiology
Nicla Porciello, Paola Grazioli, Antonio F Campese, Martina Kunkl, Silvana Caristi, Marta Mastrogiovanni, Michela Muscolini, Francesca Spadaro, Cédric Favre, Jacques A Nunès, Aldo Borroto, Balbino Alarcon, Isabella Screpanti, Loretta Tuosto
CD28 superagonistic antibodies (CD28SAb) can preferentially activate and expand immunosuppressive regulatory T cells (Treg) in mice. However, pre-clinical trials assessing CD28SAbs for the therapy of autoimmune diseases reveal severe systemic inflammatory response syndrome in humans, thereby implying the existence of distinct signalling abilities between human and mouse CD28. Here, we show that a single amino acid variant within the C-terminal proline-rich motif of human and mouse CD28 (P212 in human vs. A210 in mouse) regulates CD28-induced NF-κB activation and pro-inflammatory cytokine gene expression...
March 14, 2018: Nature Communications
Thenappan Thenappan, Mark L Ormiston, John J Ryan, Stephen L Archer
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells...
March 14, 2018: BMJ: British Medical Journal
Alicja Kalinowska-Łyszczarz, Mikołaj A Pawlak, Aleksandra Wyciszkiewicz, Katarzyna Pawlak-Buś, Piotr Leszczyński, Mariusz Puszczewicz, Włodzimierz Paprzycki, Wojciech Kozubski, Sławomir Michalak
OBJECTIVE: Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains poorly understood. Damage within the CNS is driven by the autoimmune response; however, immunopathophysiology of neuropsychiatric (NP) SLE is multifactorial. Immune cell neurotrophin production could be neuroprotective against autoimmunity-driven CNS damage, as has been shown in multiple sclerosis. The aim of this study was to establish whether immune cell neurotrophin production is associated with damage severity in NPSLE...
March 14, 2018: Neuroimmunomodulation
Marius Jacob, Kim Ohl, Tannaz Goodarzi, Sigrid Harendza, Thomas Eggermann, Christina Fitzner, Ralf-Dieter Hilgers, Anna Bolte, Jürgen Floege, Thomas Rauen, Klaus Tenbrock
BACKGROUND/AIMS: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and still constitutes one of the most important causes of end-stage renal disease. Abnormal T cell responses may play a role in IgAN pathogenesis. Co-stimulatory molecules such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are important for naive T cells to initiate and terminate immune responses. Single nucleotide polymorphisms (SNPs) in the CTLA4 gene locus are associated with several autoimmune diseases...
March 8, 2018: Kidney & Blood Pressure Research
Marilda Savoia Nascimento, Anna Maria Simonsen Stolf, Heitor Franco de Andrade Junior, Ramendra Pati Pandey, Eufrosina Setsu Umezawa
BACKGROUND: Vimentin is a main structural protein of the cell, a component of intermediate cell filaments and immersed in cytoplasm. Vimentin is mimicked by some bacterial proteins and anti-vimentin antibodies occur in autoimmune cardiac disease, as rheumatic fever. In this work we studied vimentin distribution on LLC-MK2 cells infected with T. cruzi and anti-vimentin antibodies in sera from several clinical pictures of Chagas' disease or American Trypanosomiasis, in order to elucidate any vimentin involvement in the humoral response of this pathology...
March 12, 2018: Arquivos Brasileiros de Cardiologia
Phoebe Lin
PURPOSE OF REVIEW: The intestinal commensal microbiota are important in shaping immune cell repertoire and are influenced by host genetics. Because of this intricate interaction, an intestinal dysbiosis has been associated with multiple immune-mediated polygenic diseases. This review summarizes the literature on how alterations in the intestinal microbiota contribute to immune-mediated ocular disease, and how to potentially target the gut microbiome for therapeutic benefit. RECENT FINDINGS: Several groups have demonstrated the importance of the intestinal microbiome in uveitis pathogenesis...
March 13, 2018: Current Opinion in Ophthalmology
C G Bien
The paraneoplastic and autoimmune encephalitides are now well-established entities. Detection of neural autoantibodies enables specific diagnoses, provides information on the underlying disease pathophysiology, immunological treatability and the likelihood of a tumor being the underlying cause. This is true for the "high ranking" neural antibodies that have been established in the context of circumscribed clinical images and in consideration of large control groups, have been found in the same way by other laboratories and they respond to immunotherapy...
March 13, 2018: Der Nervenarzt
James L Quinn, Gaurav Kumar, Agnieshka Agasing, Rose M Ko, Robert C Axtell
Both T cells and B cells are implicated in the pathology of multiple sclerosis (MS), but how these cells cooperate to drive disease remains unclear. Recent studies using experimental autoimmune encephalomyelitis (EAE) demonstrated that the TH17 pathway is correlated with increased numbers of ectopic B-cell follicles in the central nervous system (CNS). As follicular T helper (TFH) cells are regulators of B cell responses, we sought to examine the role of TFH cells in EAE induced by the transfer of myelin-specific TH17 cells (TH17-EAE)...
2018: Frontiers in Immunology
Hitoshi Hasegawa, Takuya Matsumoto
Dendritic cells (DCs) are a heterogeneous population playing a pivotal role in immune responses and tolerance. DCs promote immune tolerance by participating in the negative selection of autoreactive T cells in the thymus. Furthermore, to eliminate autoreactive T cells that have escaped thymic deletion, DCs also induce immune tolerance in the periphery through various mechanisms. Breakdown of these functions leads to autoimmune diseases. Moreover, DCs play a critical role in maintenance of homeostasis in body organs, especially the skin and intestine...
2018: Frontiers in Immunology
Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
Regulatory T cells (Tregs) are necessary for the maintenance of immune tolerance. Tregs are divided into two major populations: one is thymus derived and the other develops in the periphery. Among these Tregs, CD4+ CD25+ Tregs, which mainly originate in the thymus, have been extensively studied. Transcription factor Foxp3 is well known as a master regulatory gene for the development and function of CD4+ CD25+ Tregs. On the other hand, peripheral Tregs consist of distinct cell subsets including Foxp3-dependent extrathymically developed Tregs and interleukin (IL)-10-producing type I regulatory T (Tr1) cells...
2018: Frontiers in Immunology
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