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• W2750317963 abstract "Abstract Context T helper (Th)17 cells are correlated with many human autoimmune disorders, including Graves disease, and may play key roles in the pathogenesis of Graves orbitopathy (GO). Objective To study the phenotype of Th17 cells in patients with GO and healthy subjects, investigate the fibrosis and adipogenesis in orbital fibroblasts (OFs) modulated by interleukin (IL)-17A, and determine the interaction between Th17 cells and OFs. Design/Setting/Participants Blood samples and orbital tissues from GO patients and healthy controls were collected. Main Outcome Measures We conducted multicolor flow cytometry, immunohistochemical and immunofluorescent stainings, Western blotting, a PathScan intracellular signaling assay, Luminex and enzyme-linked immunosorbent assays, and protein mass spectrum. Results Interferon-γ– and IL-22–expressing Th17 cells are increased in GO patients, which are positively related to clinical activity score. Costimulatory molecules are highly expressed in GO orbits and most GO OFs are CD90+. IL-17A promotes TGF-β–induced fibrosis in CD90+ OFs but impedes 15-deoxy-Δ12,14-prostaglandin J2–induced adipogenesis in CD90− OFs. Th17 cells promote proinflammatory cytokine secretion in both CD90+ and CD90− OFs. Meanwhile, both CD90+ and CD90− OFs contribute to Th17 cell differentiation through prostaglandin E2 production, which can be attenuated by indomethacin. Furthermore, Th17 cells upregulate costimulatory molecule expression on OFs. Conclusion Our findings unravel the pathogenicity of IL-17A in the initiation and progression of GO. In-depth interpretation of the molecular basis of OFs delineated by CD90 and Th17–OF interaction will help to afford a novel approach to better therapeutic strategies for GO." @default.
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• W2750317963 date "2017-08-16" @default.
• W2750317963 modified "2023-10-17" @default.
• W2750317963 title "Regulation of Orbital Fibrosis and Adipogenesis by Pathogenic Th17 Cells in Graves Orbitopathy" @default.
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• W2750317963 doi "https://doi.org/10.1210/jc.2017-01349" @default.
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