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Treg autoimmunity

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https://www.readbyqxmd.com/read/27917204/modulation-of-immune-cells-and-th1-th2-cytokines-in-insulin-treated-type-2-diabetes-mellitus
#1
Magloire Pandoua Nekoua, Rufine Fachinan, Amidou K Atchamou, Odilon Nouatin, Daniel Amoussou-Guenou, Marcellin K Amoussou-Guenou, Kabirou Moutairou, Akadiri Yessoufou
BACKGROUND: The role of the immune system in insulin resistance associated with type 2 diabetes has been suggested. OBJECTIVES: We assessed the profile of Th1/Th2 cytokines along with the frequencies of immune cells in insulin-treated type 2 diabetic patients (T2DP). METHODS: 45 T2D patients and 43 age-matched healthy subjects were selected. Serum concentrations of T-helper type 1 (Th1) and Th2 cytokines and the frequencies of innate and adaptive immunity cells were assessed...
September 2016: African Health Sciences
https://www.readbyqxmd.com/read/27911371/development-of-stem-cell-derived-antigen-specific-regulatory-t-cells-against-autoimmunity
#2
Mohammad Haque, Kristin Fino, Praneet Sandhu, Jianxun Song
Autoimmune diseases arise due to the loss of immunological self-tolerance. Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance. Tregs represent about 5 - 10% of the mature CD4(+) T cell subpopulation in mice and humans, with about 1 - 2% of those Tregs circulating in the peripheral blood. Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs, which have a potential to be used for cell-based therapies of autoimmune diseases. Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i...
November 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27909059/the-role-of-the-histone-methyltransferase-enhancer-of-zeste-homolog-2-ezh2-in-the-pathobiological-mechanisms-underlying-inflammatory-bowel-disease-ibd
#3
Olga F Sarmento, Phyllis A Svingen, Yuning Xiong, Zhifu Sun, Adebowale O Bamidele, Angela J Mathison, Thomas C Smyrk, Asha A Nair, Michelle M Gonzalez, Mary R Sagstetter, Saurabh Baheti, Dermot P B McGovern, Jessica J Friton, Konstantinos A Papadakis, Goel Gautam, Ramnik J Xavier, Raul A Urrutia, William A Faubion
Regulatory T (Treg) cells expressing the transcription factor FOXP3 play a pivotal role in maintaining immunologic self-tolerance. We and others have previously shown that EZH2 is recruited to the FOXP3 promoter and its targets in Treg cells. To further address the role for EZH2 in Treg cellular function, we have now generated mice that lack EZH2 specifically in Treg cells (EZH2ΔFOXP3+). We find that EZH2 deficiency in FOXP3+ T cells results in lethal multi-organ autoimmunity. We further demonstrate that EZH2ΔFOXP3+ T cells lack a regulatory phenotype in vitro and secrete pro-inflammatory cytokines...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27901054/functional-defects-in-cd4-cd25-high-foxp3-regulatory-cells-in-ankylosing-spondylitis
#4
Huifang Guo, Ming Zheng, Kui Zhang, Fengfan Yang, Xin Zhang, Qing Han, Zhi-Nan Chen, Ping Zhu
Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) play a pivotal role in the preservation of self-tolerance, and Treg dysfunction has been implicated in many autoimmune diseases. Whether and how Tregs participate in the pathogenesis of ankylosing spondylitis (AS) has not been fully elucidated. Here, we investigated Treg function and found that Tregs in peripheral blood (PB) from patients with active AS had lower FoxP3 mean fluorescence intensity (MFI) than those from healthy controls and could not fully suppress naïve T cell (Tn) proliferation...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27888331/the-origin-of-dcs-and-capacity-for-immunologic-tolerance-in-central-and-peripheral-tissues
#5
REVIEW
K Sanjana P Devi, Niroshana Anandasabapathy
Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu, multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells...
November 25, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27882475/the-spatio-temporal-expression-profiles-of-cd4-t-cell-differentiation-and-function-related-genes-during-eae-pathogenesis
#6
Yingying Cai, Hu Shen, Chaoyan Qin, Jinfeng Zhou, Weiming Lai, Juping Pan, Changsheng Du
Multiple sclerosis is a CD4(+) T cell-mediated autoimmune disease of the central nervous system. The unbalance of the cytokines and transcription factors critical for CD4(+) T cell differentiation and function is probably the main reason that causes MS. We detected the mRNA expression changes of key cytokines and transcription factors which are critical for Th1, Th2, Th17, and Treg cell differentiation and function in different tissues during EAE pathogenesis. We fund that each gene not only has its own featured expression changes, but also has interaction with one another, which composes a network of immunity...
November 24, 2016: Inflammation
https://www.readbyqxmd.com/read/27882473/foxp3-regulatory-t-cell-and-autoimmune-diseases
#7
REVIEW
Jin-Hui Tao, Miao Cheng, Jiang-Ping Tang, Qin Liu, Fan Pan, Xiang-Pei Li
Regulatory T cells (Tregs) represent a cell type that promotes immune tolerance to autologous components and maintains immune system homeostasis. The abnormal function of Tregs is relevant to the pathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune diseases. Therefore, therapeutic modulation of Tregs could be a potent means of treating autoimmune diseases. Human Tregs are diverse, however, and not all of them have immunosuppressive effects. Forkhead box P3 (Foxp3), a pivotal transcription factor of Tregs that is crucial in maintaining Treg immunosuppressive function, can be expressed heterogeneously or unstably across Treg subpopulations...
November 24, 2016: Inflammation
https://www.readbyqxmd.com/read/27880975/ror%C3%AE-t-expression-in-tregs-promotes-systemic-lupus-erythematosus-via-il-17-secretion-alteration-of-treg-phenotype-and-suppression-of-th2-responses
#8
Malte A Kluger, Anna Nosko, Torben Ramcke, Boeren Goerke, Matthias C Meyer, Claudia Wegscheid, Michael Luig, Gisa Tiegs, Rolf A K Stahl, Oliver M Steinmetz
Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex and poorly understood immuno-pathogenesis. However, a pathogenic role for the Th17 axis was demonstrated by many studies, while Tregs were shown to mediate protection. Recently, we and others characterized a novel and independent T cell population expressing both, the Treg characteristic transcription factor Foxp3 and the Th17 defining RORγt. Studies in a model of acute glomerulonephritis unveiled potent regulatory, but in addition also pro-inflammatory functions of RORγt(+) Foxp3(+) Tregs...
November 23, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27880731/smad4-in-t-cells-plays-a-protective-role-in-the-development-of-autoimmune-sj%C3%A3-gren-s-syndrome-in-the-nonobese-diabetic-mouse
#9
Donghee Kim, Jae Young Kim, Hee-Sook Jun
We investigated the role of Smad4, a signaling molecule of the TGF-beta pathway, in T cells on the pathology of Sjögren's syndrome (SS) in nonobese diabetic (NOD) mice, an animal model of SS. T cell-specific Smad4-deleted (Smad4fl/fl,CD4-Cre; Smad4 tKO) NOD mice had accelerated development of SS compared with wild-type (Smad4+/+,CD4-Cre; WT) NOD mice, including increased lymphocyte infiltration into exocrine glands, decreased tear and saliva production, and increased levels of autoantibodies at 12 weeks of age...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27878211/liraglutide-enhances-the-efficacy-of-human-mesenchymal-stem-cells-in-preserving-islet-%C3%AE-cell-function-in-severe-non-obese-diabetic-mice
#10
Li-Rong Li, Xiao-Lei Jia, Hui Hui, Jie Zhang, Ying Liu, Wei-Juan Cui, Qian-Yue Xu, Da-Long Zhu
Glucagon-like peptide 1 (GLP-1) can promote islet β-cell replication and function, and mesenchymal stem cells (MSCs) can inhibit T cell autoimmunity. This study aimed at testing the dynamic distribution of infused human MSCs and therapeutic effect of combined MSCs and Liraglutide, a long-acting GLP-1 analogue, on preserving β-cell function in severe non-obese diabetic (NOD) mice. We found that infused MSCs accumulated in the pancreas at 4 weeks post infusion, which was not affected by Liraglutide treatment...
November 17, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27872297/singular-role-for-t-bet-cxcr3-regulatory-t-cells-in-protection-from-autoimmune-diabetes
#11
Tze Guan Tan, Diane Mathis, Christophe Benoist
Foxp3(+) regulatory T (Treg) cells are crucial for restraining inflammation in a variety of autoimmune diseases, including type 1 diabetes (T1D). However, the transcriptional and functional phenotypes of Treg cells within the pancreatic lesion remain poorly understood. Here we characterized pancreas-infiltrating Treg cells in the NOD mouse model of T1D and uncovered a substantial enrichment of the Treg subpopulation expressing the chemokine receptor CXCR3. Accumulation of CXCR3(+) Treg cells within pancreatic islets was dependent on the transcription factor T-BET, and genetic ablation of T-BET increased the onset and penetrance of disease, abrogating the sex bias normally seen in the NOD model...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27867385/expanding-diversity-in-molecular-structures-and-functions-of-the-il-6-il-12-heterodimeric-cytokine-family
#12
REVIEW
Hideaki Hasegawa, Izuru Mizoguchi, Yukino Chiba, Mio Ohashi, Mingli Xu, Takayuki Yoshimoto
The interleukin (IL)-6/IL-12 family cytokines have pleiotropic functions and play critical roles in multiple immune responses. This cytokine family has very unique characteristics in that they comprise two distinct subunits forming a heterodimer and each cytokine and receptor subunit shares with each other. The members of this cytokine family are increasing; currently, there are more than six cytokines, including the tentatively named cytokines IL-Y (p28/p40), IL-12 (p35/p40), IL-23 (p19/p40), IL-27 [p28/Epstein-Barr virus-induced protein 3 (EBI3)], IL-35 (p35/EBI3), and IL-39 (p19/EBI3)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27865709/defective-splicing-of-the-background-k-channel-k2p5-1-by-the-pre-mrna-splicing-inhibitor-pladienolide-b-in-lectin-activated-mouse-splenic-cd4-t-cells
#13
Kazutaka Tagishi, Ayaka Shimizu, Kyoko Endo, Hiroaki Kito, Satomi Niwa, Masanori Fujii, Susumu Ohya
The two-pore domain K(+) channel K2P5.1 has been implicated in the pathogenesis of autoimmune diseases. We investigated the changes in K2P5.1 activity caused by a defect in normal pre-mRNA splicing in concanavalin A-activated mouse splenic CD4(+) T cells. The pre-mRNA splicing inhibitor, pladienolide B (1 μM) markedly decreased full-length K2P5.1 transcription in activated CD4(+) T cells, resulting in the disappearance of K2P5.1 activity and an imbalance in Th17 and Treg cytokines. These results suggest that the defect in K2P5...
November 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27863545/porcine-treg-depletion-with-a-novel-diphtheria-toxin-based-anti-human-ccr4-immunotoxin
#14
Zhaohui Wang, Nalu Navarro-Alvarez, Jigesh A Shah, Huiping Zhang, Qi Huang, Qian Zheng, Joren C Madsen, David H Sachs, Christene A Huang, Zhirui Wang
Regulatory T cells (Tregs) are known to play an important role in immunoregulation and have been shown to facilitate induction of transplantation tolerance. Chemokine (C-C motif) receptor 4 (CCR4) is expressed on the surface of effector Tregs involved in controlling alloimmune and autoimmune responses. Recently we have developed a novel diphtheria-toxin based anti-human CCR4 immunotoxin for depleting CCR4(+) cells in vivo. In this study, we have demonstrated that the anti-human CCR4 immunotoxin bound to porcine lymphocytes including CD4(+)FoxP3(+) Tregs...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27862977/low-dose-il-2-increase-regulatory-t-cells-and-elevate-platelets-in-a-patient-with-immune-thrombocytopenia
#15
Jiakui Zhang, Yanjie Ruan, Yuanyuan Shen, Qianshan Tao, Huiping Wang, Lili Tao, Yin Pan, Huizi Fang, Yiping Wang, Zhimin Zhai
Immune thrombocytopenia (ITP) is an autoimmune disorder in which its immune system destroy platelets and lead to haemorrhage symptom. Recent studies have found that regulatory T cells (Tregs) in peripheral blood, bone marrow, and spleen were reduced in ITP patients and recovered after effective ITP therapy. Low-dose Interleukin-2 (IL-2) has been reported recently to increase Tregs and used to treat autoimmune disease including graft-versus-host disease (GVHD) after organ transplantation and HCV-related autoimmune vasculitis...
November 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27859048/%C3%AE-cell-specific-il-35-therapy-suppresses-ongoing-autoimmune-diabetes-in-nod-mice
#16
Fatima Manzoor, Mark C Johnson, Chengwen Li, R Jude Samulski, Bo Wang, Roland Tisch
IL-35 is a recently identified cytokine exhibiting potent immunosuppressive properties. The therapeutic potential and effects of IL-35 on pathogenic T effector (Teff) cells and Foxp3(+) Treg cells, however, are ill-defined. We tested the capacity of IL-35 to suppress ongoing autoimmunity in NOD mice. For this purpose, an adeno-associated virus vector in which IL-35 transgene expression is selectively targeted to β cells via an insulin promoter (AAV8mIP-IL35) was used. AAV8mIP-IL35 vaccination of NOD mice at a late preclinical stage of type 1 diabetes (T1D) suppressed β-cell autoimmunity and prevented diabetes onset...
November 8, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27855396/imbalance-of-th17-treg-in-different-subtypes-of-autoimmune-thyroid-diseases
#17
Cui Li, Jianghong Yuan, Yuan-Feng Zhu, Xiang-Ju Yang, Qiong Wang, Jian Xu, Shuang-Tao He, Jin-An Zhang
AIMS: To clarify the imbalance of Th17/Treg in different subtypes of autoimmune thyroid diseases (AITDs) including Graves' disease(GD), Hashimoto's thyroiditis(HT) and Graves' ophthalmopathy (GO). METHODS: 47 patients with AITD (including 16 GD, 15 HT, and 16 GO) and 12 healthy controls were enrolled in this study. The percentages of Th17 and Treg cells, the ratio of Th17/Treg, as well as their related transcription factors RORγt and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry and real-time quantitative PCR Results: Compared with those in control group, the percentage of CD4+IL-17+T cell(Th17) and the mRNA expression of its transcription factor RORγt were higher in PBMCs of AITDs (P<0...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27854550/expression-and-function-of-the-co-stimulatory-receptor-slamf1-is-altered-in-lymphocytes-from-patients-with-autoimmune-thyroiditis
#18
Marlen Vitales-Noyola, Ana M Ramos-Levi, Ana Serrano-Somavilla, Rebeca Hernández-Martínez, Miguel Sampedro-Nuñez, Carmelina Di Pasquale, Roberto González-Amaro, Mónica Marazuela
CONTEXT: SLAMF1 is a co-stimulatory receptor that is expressed by most immune cells. Its role in Autoimmune Thyroid Disease (AITD) is not well known. OBJECTIVE: To analyze the expression and function of the co-stimulatory receptor SLAMF1 in lymphocytes of patients with AITD. DESIGN: Cross-sectional, prospective, single-center. SETTING: Department of Endocrinology, Hospital Universitario Princesa. PATIENTS: 28 patients with AITD (17 with Graves' disease and 11 with Hashimoto's thyroiditis) and 21 controls...
November 17, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27851889/a-novel-method-for-assaying-human-regulatory-t-cell-direct-suppression-of-b-cell-effector-function
#19
Elizabeth Weingartner, Jean-Paul Courneya, Achsah Keegan, Amit Golding
We have established a highly reproducible and reliable protocol for testing human regulatory T cell function in suppressing IgM production from an immature human B cell line. The autoreactive Ramos B cell line provides a stable reporter of B cell effector function that can be tested by a straight-forward IgM ELISA. Tregs from healthy volunteers display a range of ability for suppressing baseline IgM production in a contact- and death-independent manner. Having established the normal range for human Treg direct suppression of B cell effector function, it will now be possible to efficiently test Tregs from various autoimmune conditions in which B cell hyperactivity and secretion of auto-antibodies are a hallmark of disease...
November 13, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27845855/lactobacillus-salivarius-isolated-from-patients-with-rheumatoid-arthritis-suppresses-collagen-induced-arthritis-and-increases-treg-frequency-in-mice
#20
Xiaofei Liu, Juan Zhang, Qinghua Zou, Bing Zhong, Heng Wang, Fangxiang Mou, Like Wu, Yongfei Fang
Previously, we demonstrated that Lactobacillus salivarius was more abundant in patients with rheumatoid arthritis (RA), an inflammatory autoimmune disease wherein the gut microbiota is altered, than in healthy individuals. However, the effect of L. salivarius in RA is unclear. Hence, we investigated the effect of L. salivarius isolated from patients with RA on collagen-induced arthritis (CIA) in mice. L. salivarius UCC118 or L. plantarum WCFS1 isolated from patients with RA was administered orally for 5 weeks, starting from 2 weeks before the induction of arthritis in DBA/1 mice...
December 2016: Journal of Interferon & Cytokine Research
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