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Treg autoimmunity

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https://www.readbyqxmd.com/read/29158419/ultraviolet-b-induced-maturation-of-cd11b-type-langerin-dendritic-cells-controls-the-expansion-of-foxp3-regulatory-t-cells-in-the-skin
#1
Sayuri Yamazaki, Mizuyu Odanaka, Akiko Nishioka, Saori Kasuya, Hiroaki Shime, Hiroaki Hemmi, Masaki Imai, Dieter Riethmacher, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita
Skin dendritic cells (DCs) are divided into several subsets with distinctive functions. This study shows a previously unappreciated role of dermal CD11b-type Langerin(-) DCs in maintaining immunological self-tolerance after UVB exposure. After UVB exposure, dermal CD11b-type Langerin(-) DCs upregulated surface CD86 expression, induced proliferation of Foxp3(+) regulatory T (Treg) cells without exogenous Ags, and upregulated a set of genes associated with immunological tolerance. This Treg-expansion activity was significantly hampered by CD80/CD86 blockade in vivo...
November 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29158050/autoimmune-thyroid-diseases-and-th17-treg-lymphocytes
#2
REVIEW
Shiying Shao, Xuefeng Yu, Liya Shen
Years of researches have demonstrated that the imbalance of Th17 and Tregs contribute to the thyroid autoimmunity and the severity of autoimmune thyroid disease (AITD). The underlying mechanism comprises inherent genetic predisposition, abnormality of Th17 and Treg related biological molecules, and gut microbiota disorder. New therapeutic strategies have been developed to improve the Th17/Treg equilibrium, including regulation of intracellular signaling pathways, neutralization of Th17-related cytokines, as well as manipulation of Th17 and Treg specific transcription factors...
November 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29155454/harnessing-the-power-of-regulatory-t-cells-to-control-autoimmune-diabetes-overview-and-perspective
#3
REVIEW
Hua Yu, Ricardo Paiva, Richard A Flavell
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease resulting in islet β-cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Although the mechanisms that initiate T1D still remain elusive, a breakdown of immune tolerance between effector T cells (Teff) and regulatory T cells (Treg) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of Treg in the hope of specifically hampering the pathogenic Teff activity...
November 20, 2017: Immunology
https://www.readbyqxmd.com/read/29155098/orai1-mutations-abolishing-store-operated-ca-2-entry-cause-anhidrotic-ectodermal-dysplasia-with-immunodeficiency-eda-id
#4
Jayson Lian, Mario Cuk, Sascha Kahlfuss, Lina Kozhaya, Martin Vaeth, Frédéric Rieux-Laucat, Capucine Picard, Melina J Benson, Antonia Jakovcevic, Karmen Bilic, Iva Martinac, Peter Stathopulos, Imre Kacskovics, Thomas Vraetz, Carsten Speckmann, Stephan Ehl, Thomas Issekutz, Derya Unutmaz, Stefan Feske
BACKGROUND: Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels is an essential signaling pathway in many cell types. CRAC channels are formed by ORAI1, ORAI2 and ORAI3 proteins and activated by stromal interaction molecule 1 (STIM1) and STIM2. Mutations in ORAI1 and STIM1 genes that abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by autoimmunity and non-immunological symptoms. OBJECTIVE: Molecular and immunological analysis of patients with CID, anhidrosis and ectodermal dysplasia of unknown etiology...
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29149782/frequency-of-circulatory-regulatory-immune-cells-in-iranian-patients-with-type-1-diabetes
#5
Tahereh Khamehchian, Eqlim Nemati, Marziyeh Jazayeri, Shirin Azimi, Hassan Nikoueinejad, Hossein Akbari, Behnaz Irandoust
Type 1 diabetes (T1D) is the result of the autoimmune destruction of insulin-producing beta cells. Regulatory T cells (Tregs) and plasmacytoid dendritic cells (PDCs) act as mediators of peripheral tolerance. We investigated the possible alterations of such cells in peripheral blood of patients with T1D compared to normal individuals. This comparison may lead to a better understanding of the immunopathogenesis processes involved in T1D. 92 participants, including 49 patients with T1D and 43 healthy controls were studied...
October 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29149778/the-changes-of-th17-treg-and-related-cytokines-il-17-il-23-il-10-and-tgf-%C3%AE-in-respiratory-syncytial-virus-bronchiolitis-rat-model
#6
Meng Gao, Liang-Xiao Liu, Fu-Ling Wu, Xuejing Zhang, Ying-Ying Li, Tao Shi, De-Zhi Li, Ting-Ting Han
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization that lead to high morbidity and mortality among young infants. T helper 17 (Th17) cells and regulatory T cells (Tregs) play essential roles in the pathogenesis of autoimmune, cancer, and inflammatory diseases. However, whether changes in T-cell subsets are related to the systemic immune responses in RSV-caused bronchiolitis merit further investigation. Three-week-old Sprague Dawley (SD) rats were randomly divided into the normal control (NC) and RSV bronchiolitis (RSV-B) groups...
October 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29141218/reciprocal-expression-of-il-35-and-il-10-defines-two-distinct-effector-treg-subsets-that-are-required-for-maintenance-of-immune-tolerance
#7
Xundong Wei, Jianhua Zhang, Qianchong Gu, Man Huang, Wei Zhang, Jie Guo, Xuyu Zhou
Regulatory T cells (Tregs) can exert their functions through multiple suppressive mechanisms; however, it is unclear how Tregs exactly employ these mechanisms. In this study, we found that interleukin-35 (IL-35)-producing Tregs were a distinct effector population from the IL-10-producing subset. We also revealed that these two subsets of effector Tregs have different transcription factor dependency. Terminal differentiation regulator Blimp1 was only critical for IL-10 production, but not for IL-35; Foxp3 was essential for IL-35 but dispensable for IL-10 production...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29129697/dual-mechanisms-for-balancing-th17-and-treg-cell-fate-by-creb
#8
Antony Symons, Wenjun Ouyang
Th17 cells, which express the cytokine IL-17A, and master regulator RORγt, are important in the inflammatory response to fungal and bacterial pathogens, but also have a pathogenic role in many inflammatory disorders. In contrast, regulatory T cells (Treg), expressing the Foxp3 transcription factor, have a suppressive function and can dampen an immune response. The appropriate balance of these distinct effector functions is critical for an effective immune response and autoimmunity can arise if this process goes awry...
November 2017: EBioMedicine
https://www.readbyqxmd.com/read/29126851/ccr6-signaling-inhibits-suppressor-function-of-induced-treg-during-gut-inflammation
#9
Neeraja Kulkarni, Heikrujam Thoihen Meitei, Sandip Ashok Sonar, Praveen Kumar Sharma, Vikkarasan Rehman Mujeeb, Sharad Srivastava, Ramanamurthy Boppana, Girdhari Lal
CCR6 is a G protein-coupled receptor (GPCR) that binds to a specific chemokine, CCL20. The role of CCR6-CCL20 is very well studied in the migration of immune cells, but the non-chemotaxis functions of CCR6 signaling were not known. Here, we show that during gut inflammation, the frequency of Foxp3(+)CD4(+) T cells (Tregs) reduced in the secondary lymphoid tissues and CCR6(+) Tregs enhanced the expression of RORγt. The peripheral blood mononuclear cells (PBMCs) of ulcerative colitis (UC) patients showed lower percentages of Foxp3(+)CD4(+) T cells, as compared to healthy individuals, with CCR6(+) Tregs showing higher RORγt expression as compared to CCR6(-)Tregs...
November 7, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29126272/generation-of-alloantigen-specific-induced-treg-stabilized-by-vitamin-c-treatment-and-its-application-for-prevention-of-acute-graft-versus-host-disease-model
#10
Hidenori Kasahara, Taisuke Kondo, Hiroko Nakatsukasa, Shunsuke Chikuma, Minako Ito, Makoto Ando, Yutaka Kurebayashi, Takashi Sekiya, Taketo Yamada, Shinichiro Okamoto, Akihiko Yoshimura
Antigen-specific regulatory T cells (Tregs) possess the potential to reduce excess immune responses in autoimmune diseases, allergy, rejection after organ transplantation, and graft-versus-host disease (GVHD) in hematopoietic stem-cell transplantation. Although in vitro-expanded antigen-specific induced Tregs (iTregs) have been considered to be a promising therapeutic agent against such excessive immune reactions, the instability of iTregs after transfer is a fundamental problem in their clinical application...
November 4, 2017: International Immunology
https://www.readbyqxmd.com/read/29123529/t-cell-mediated-chronic-inflammatory-diseases-are-candidates-for-therapeutic-tolerance-induction-with-heat-shock-proteins
#11
REVIEW
Ariana Barbera Betancourt, Qingkang Lyu, Femke Broere, Alice Sijts, Victor P M G Rutten, Willem van Eden
Failing immunological tolerance for critical self-antigens is the problem underlying most chronic inflammatory diseases of humans. Despite the success of novel immunosuppressive biological drugs, the so-called biologics, in the treatment of diseases such rheumatoid arthritis (RA) and type 1 diabetes, none of these approaches does lead to a permanent state of medicine free disease remission. Therefore, there is a need for therapies that restore physiological mechanisms of self-tolerance. Heat shock proteins (HSPs) have shown disease suppressive activities in many models of experimental autoimmune diseases through the induction of regulatory T cells (Tregs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29123521/good-manufacturing-practice-compliant-production-and-lot-release-of-ex-vivo-expanded-regulatory-t-cells-as-basis-for-treatment-of-patients-with-autoimmune-and-inflammatory-disorders
#12
Manuel Wiesinger, Diane Stoica, Susanne Roessner, Carmen Lorenz, Anika Fischer, Raja Atreya, Clemens F Neufert, Imke Atreya, Alexander Scheffold, Beatrice Schuler-Thurner, Markus F Neurath, Gerold Schuler, Caroline J Voskens
In recent years, the exploration of regulatory T cell (Treg)-based cellular therapy has become an attractive strategy to ameliorate inflammation and autoimmunity in various clinical settings. The main obstacle to the clinical application of Treg in human is their low number circulating in peripheral blood. Therefore, ex vivo expansion is inevitable. Moreover, isolation of Treg bears the risk of concurrent isolation of unwanted effector cells, which may trigger or deteriorate inflammation upon adoptive Treg transfer...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29123516/avidity-and-bystander-suppressive-capacity-of-human-regulatory-t-cells-expressing-de-novo-autoreactive-t-cell-receptors-in-type-1-diabetes
#13
Wen-I Yeh, Howard R Seay, Brittney Newby, Amanda L Posgai, Filipa Botelho Moniz, Aaron Michels, Clayton E Mathews, Jeffrey A Bluestone, Todd M Brusko
The ability to alter antigen specificity by T-cell receptor (TCR) or chimeric antigen receptor (CAR) gene transfer has facilitated personalized cellular immune therapies in cancer. Inversely, this approach can be harnessed in autoimmune settings to attenuate inflammation by redirecting the specificity of regulatory T cells (Tregs). Herein, we demonstrate efficient protocols for lentiviral gene transfer of TCRs that recognize type 1 diabetes-related autoantigens with the goal of tissue-targeted induction of antigen-specific tolerance to halt β-cell destruction...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29121519/iguratimod-ameliorates-inflammatory-responses-by-modulating-the-th17-treg-paradigm-in-dextran-sulphate-sodium-induced-murine-colitis
#14
Xue-Pei Jiang, Xie-Lin Huang, Zao-Peng Yang, Shun-Cai Wang, Wei Xie, Lei Miao, Li Tang, Zhi-Ming Huang
Inflammatory bowel disease (IBD) is an autoimmune disease with an abnormal and persistent immune response. Iguratimod, a novel anti-rheumatic drug, exhibits anti-inflammatory effects and regulates immune response. The role of iguratimod in intestinal mucosal inflammation and immunity has not been examined. The aim of this study was to investigate whether iguratimod ameliorates dextran sulphate sodium (DSS)-induced murine colitis and its potential regulatory mechanism. Murine colitis was induced by administering 2...
November 6, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29120583/role-of-lymphocyte-subpopulations-in-the-immunopathogenesis-of-psoriasis-and-the-effect-of-narrow-band-uvb-phototherapy-on-the-immunological-profile-of-psoriasis-patients
#15
Mona Fattouh, Asmaa N El-Din, Mohammed A El-Hamd
Psoriasis is one of the most common chronic, inflammatory, T-cell-mediated autoimmune diseases. Narrow-band UVB (NB-UVB) therapy is widely used in the treatment of psoriasis; however, its mechanism of action is still not well understood. The objective of this study was to investigate the circulating T-lymphocyte subpopulations in psoriasis patients before and after NB-UVB, to get insights into the mechanism of NB-UVB in the treatment of psoriasis. The severity of psoriasis was assessed by means of the Psoriasis Area and Severity Index (PASI-score)...
January 2017: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/29118761/immunological-and-clinical-effect-of-diet-modulation-of-the-gut-microbiome-in-multiple-sclerosis-patients-a-pilot-study
#16
Marina Saresella, Laura Mendozzi, Valentina Rossi, Franca Mazzali, Federica Piancone, Francesca LaRosa, Ivana Marventano, Domenico Caputo, Giovanna E Felis, Mario Clerici
Pathogenesis of autoimmune disorders, including multiple sclerosis (MS), has been linked to an alteration of the resident microbial commensal community and of the interplay between the microbiota and the immune system. Dietary components such as fiber, acting on microbiota composition, could, in principle, result in immune modulation and, thus, could be used to obtain beneficial outcomes for patients. We verified this hypothesis in a pilot study involving two groups of clinically similar relapsing-remitting (RR) MS patients who had undergone either a high-vegetable/low-protein diet (HV/LP diet group; N = 10) or a "Western Diet" (WD group; N = 10) for at least 12 months...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29116141/constitutive-expression-of-nf-%C3%AE%C2%BAb-inducing-kinase-in-regulatory-t-cells-impairs-suppressive-function-and-promotes-instability-and-pro-inflammatory-cytokine-production
#17
Fanny Polesso, Minhazur Sarker, Arian Anderson, David C Parker, Susan E Murray
CD4(+)Foxp3(+) regulatory T cells (Tregs) are indispensable negative regulators of immune responses. To understand Treg biology in health and disease, it is critical to elucidate factors that affect Treg homeostasis and suppressive function. Tregs express several costimulatory TNF receptor family members that activate non-canonical NF-κB via accumulation of NF-κB inducing kinase (NIK). We previously showed that constitutive NIK expression in all T cells causes fatal multi-organ autoimmunity associated with hyperactive conventional T cell responses and poor Treg-mediated suppression...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29112894/study-the-effects-of-mesenchymal-stem-cell-conditioned-medium-injection-in-mouse-model-of-acute-colitis
#18
Sedigheh Pouya, Maryam Heidari, Kaveh Baghaei, Hamid Asadzadeh Aghdaei, Afshin Moradi, Saeed Namaki, Mohammad Reza Zali, Seyed Mahmoud Hashemi
BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is an autoimmune-inflammatory disorder that results in inflammatory responses in individuals who are genetically susceptible. Uncontrolled inflammation in Crohn's disease (CD) or Ulcerative colitis (UC) affects the patient quality of life. Current therapies are not completely effective while cell therapy, especially the treatment with mesenchymal stem cells (MSCs) absorb lots of attention due to its immunomodulatory properties. So, we examined the effects of mesenchymal stem cells-conditioned medium (MSC-CM) in the experimental model of acute colitis...
November 4, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29109251/metabolic-control-of-regulatory-t-cell-treg-survival-and-function-by-lkb1
#19
Nanhai He, Weiwei Fan, Brian Henriquez, Ruth T Yu, Annette R Atkins, Christopher Liddle, Ye Zheng, Michael Downes, Ronald M Evans
The metabolic programs of functionally distinct T cell subsets are tailored to their immunologic activities. While quiescent T cells use oxidative phosphorylation (OXPHOS) for energy production, and effector T cells (Teffs) rely on glycolysis for proliferation, the distinct metabolic features of regulatory T cells (Tregs) are less well established. Here we show that the metabolic sensor LKB1 is critical to maintain cellular metabolism and energy homeostasis in Tregs. Treg-specific deletion of Lkb1 in mice causes loss of Treg number and function, leading to a fatal, early-onset autoimmune disorder...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29102469/a-sweet-deal-for-diabetes
#20
Matteo Villa, Jing Qiu, Erika L Pearce
Sugars have pathogenic roles in diabetes. In Nature Medicine, Zhang et al. revisit this dogma and show that mannose induces the generation of regulatory T (Treg) cells. The immunoregulatory effect of mannose not only prevented the onset of autoimmune diabetes but also blocked disease progression in new-onset diabetic mice.
November 1, 2017: Trends in Endocrinology and Metabolism: TEM
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