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Interleukin\u20106 (IL\u20106) is secreted by many cell types, including macrophages and synovial fibroblasts. It induces the differentiation and function of Th17 cells that can increase lymphocytic infiltration in the joint. LMT\u201028 can suppress IL\u20106 signalling through direct binding to glycoprotein\u2010130 and alleviate inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. The purpose of this study was to assess whether LMT\u201028 could potently inhibit Th17 differentiation and to determine the mechanism involved in the attenuating effect of LMT\u201028 on rheumatoid arthritis through the IL\u20106 signalling pathway. LMT\u201028 reduced the arthritis score and showed protective effects against bone and cartilage destruction in collagen\u2010induced arthritis (CIA) mice. In mice with CIA, LMT\u201028 markedly decreased serum levels of IL\u20106, TNF and IL\u20101\u03b2 compared to vehicle control. Moreover, LMT\u201028 attenuated Th17 cell activation in lymph nodes of CIA mice. We demonstrated that LMT\u201028 suppressed differentiation of Th17 in mouse splenocytes and human peripheral blood mononuclear cells (PBMCs). Additionally, LMT\u201028 inhibited phosphorylation of GP130, STAT3 and ERK induced by Hyper\u2010IL\u20106 in human fibroblast\u2010like synoviocytes (FLS). Collectively, these results suggest that LMT\u201028 can inhibit differentiated\/activated\u2010Th17 cells in rheumatoid arthritis by blocking activation of the STAT3 pathway. LMT\u201028 can attenuate rheumatoid arthritis by inhibiting differentiation\/activation of Th17 cells and suppressing the proliferation and signalling activation of the IL\u20106\/solubleIL\u20106 receptor complex stimulated FLS.<\/jats:p>","DOI":"10.1111\/1440-1681.13215","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T18:20:09Z","timestamp":1574187609000},"page":"628-639","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A directly GP130\u2010targeting small molecule ameliorates collagen\u2010induced arthritis (CIA) by inhibiting IL\u20106\/GP130 signalling and Th17 differentiation"],"prefix":"10.1111","volume":"47","author":[{"given":"Yeon\u2010Hwa","family":"Park","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacoimmunology Integrated Research Institute of Pharmaceutical Sciences College of Pharmacy The Catholic University of Korea Bucheon 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