Small molecules targeting RORγt inhibit autoimmune disease by suppressing Th17 cell differentiation
نویسندگان
چکیده
منابع مشابه
Small Molecule Inhibitors Targeting the Th17 Cell Transcription Factor RORγt for the Treatment of Autoimmune Diseases
Naïve CD4+ T helper cells can differentiate into Th1, Th2, Th17, T regulatory, Th9 and Th22 cells. Th1 cells are characterized by their production of IFNγ but not IL-4 and IL-5 while Th2 cells are characterized by their expression of IL-4 and IL-5 but not IFNγ. T-bet and GATA3 are the master transcription factors for Th1 and Th2 cells, respectively [1]. Th1 cells mediate cellular immunity again...
متن کاملIdentification of Tetraazacyclic Compounds as Novel Potent Inhibitors Antagonizing RORγt Activity and Suppressing Th17 Cell Differentiation
CD4+ T-helper cells that produce interleukin-17 (Th17 cells) are characterized as pathological T-helper cells in autoimmune diseases. Differentiation of human and mouse Th17 cells requires a key transcription regulator, retinoic acid receptor-related orphan receptor γt (RORγt), which is a potential therapeutic target for autoimmune diseases. To develop a therapeutic agent for Th17-mediated auto...
متن کامل3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation
Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 ce...
متن کاملTargeting Th17 Cells with Small Molecules and Small Interference RNA
T helper 17 (Th17) cells play a central role in inflammatory and autoimmune diseases via the production of proinflammatory cytokines interleukin- (IL-) 17, IL-17F, and IL-22. Anti-IL-17 monoclonal antibodies show potent efficacy in psoriasis but poor effect in rheumatoid arthritis (RA) and Crohn's disease. Alternative agents targeting Th17 cells may be a better way to inhibit the development an...
متن کاملIL-6-mediated Th17 differentiation through RORγt is essential for the initiation of experimental autoimmune myocarditis.
AIMS Interleukin (IL)-17-producing helper T (Th17) cells have been proposed to participate in the pathogenesis of chronic inflammation, such as autoimmune myocarditis. IL-6 gene ablation confers the resistance to experimental autoimmune myocarditis (EAM). In this study, we have addressed the pathological roles of IL-6 in the regulation of Th17 cells in EAM. METHODS AND RESULTS To induce EAM, ...
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ژورنال
عنوان ژورنال: Cell Death & Disease
سال: 2020
ISSN: 2041-4889
DOI: 10.1038/s41419-020-02891-2