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However, the underlying mechanism needs further study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Flow cytometry, immunofluorescence, enzyme linked immunosorbent assay \uff08ELISA\uff09, and quantitative real\u2010time polymerase chain reaction \uff08qRT\u2010PCR\uff09 reveal the obvious inhibitory effects of QU on Th17 cell differentiation in arthritic mice. More importantly, QU markedly limits the development of Th17 cell polarization, which is virtually compromised by the treatment with peroxisome proliferator activated receptor \u03b3 (PPAR\u03b3) inhibitor GW9662 and knockdown of PPAR\u03b3. Additionally, molecular dynamics simulation and immunofluorescence exhibit QU directly binds to PPAR\u03b3 and increases PPAR\u03b3 nuclear translocation. Besides, QU confers its moderation effect on suppressor of cytokine signaling protein (SOCS3)\/signal transducer and activator of transcription 3 (STAT3) axis partially depending on PPAR\u03b3. Furthermore, coimmunoprecipitation shows QU redistributes the corepressor silencing mediator for retinoid and thyroid\u2010hormone receptors (SMRT) from PPAR\u03b3 to STAT3. Finally, the inhibition of Th17 response and the antiarthritic effect of QU are nullified by GW9662 treatment in arthritic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>QU targets PPAR\u03b3 and consequently inhibits Th17 cell differentiation by dual inhibitory activity of STAT3 to exert antiarthritic effect. The findings facilitate its development and put forth a stage for uncovering the mechanism of other naturally occurring compounds with chemical structures similar to QU.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202100826","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T15:38:56Z","timestamp":1649173136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Quercetin Impedes Th17 Cell Differentiation to Mitigate Arthritis Involving PPAR\u03b3\u2010Driven Transactivation of SOCS3 and Redistribution Corepressor SMRT from PPAR\u03b3 to STAT3"],"prefix":"10.1002","volume":"66","author":[{"given":"Yan","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"},{"name":"Department of Pharmacy The Third People's Hospital of Chengdu The Affiliated Hospital of Southwest Jiaotong University The Second Chengdu Hospital Affiliated to Chongqing Medical University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao\u2010na","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences &amp; 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