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Targeting pathogenic Th17 cells and their associated molecules is emerging as a promising strategy to treat and reverse RA. Here, we demonstrate that IL\u20103 inhibits the differentiation of Th17 cells and promotes the development of Treg cells in IL\u20102\u2010dependent manner. In IL\u20102 KO mice, we observed that IL\u20103 has no effect on differentiation of both Th17 and Treg cells. In addition, IL\u20103 decreases pathogenic IL\u201017A<jats:sup>+<\/jats:sup>TNF\u2010\u03b1<jats:sup>+<\/jats:sup>, IL\u201017A<jats:sup>+<\/jats:sup>IFN\u2010\u03b3<jats:sup>+<\/jats:sup> and IL\u201023R<jats:sup>+<\/jats:sup> Th17 cells, secretion of GM\u2010CSF and IFN\u2010\u03b3, and osteoclastogenesis when presented in the culture together with Th17 polarizing cytokines. Mechanistically, IL\u20103 regulates the development of Th17 cells through the inhibition of STAT3 phosphorylation. IL\u20103 treatment significantly decreases the pathogenic Th17 cell responses and arthritic scores in the mouse model of RA. Importantly, IL\u20103 inhibits the differentiation of human Th17 cells. Thus, our results suggest a novel therapeutic role of IL\u20103 in the regulation of Th17 cell\u2010mediated pathophysiology of RA.<\/jats:p>","DOI":"10.1002\/eji.202149674","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T18:50:18Z","timestamp":1662663018000},"page":"1842-1858","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["IL\u20103 regulates the differentiation of pathogenic Th17 cells"],"prefix":"10.1002","volume":"52","author":[{"given":"Lekha","family":"Rani","sequence":"first","affiliation":[{"name":"Bone and Cartilage Research Laboratory National Centre for Cell Science  Pune 411007 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Kumar","sequence":"additional","affiliation":[{"name":"Bone and Cartilage Research Laboratory National Centre for Cell Science  Pune 411007 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juilee","family":"Karhade","sequence":"additional","affiliation":[{"name":"Bone and Cartilage Research Laboratory National Centre for Cell Science  Pune 411007 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garima","family":"Pandey","sequence":"additional","affiliation":[{"name":"Bone and Cartilage Research Laboratory National Centre for Cell Science  Pune 411007 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrita","family":"Guha","sequence":"additional","affiliation":[{"name":"Bone and Cartilage Research Laboratory National Centre for Cell Science  Pune 411007 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyan C.","family":"Mishra","sequence":"additional","affiliation":[{"name":"Bone and Cartilage Research Laboratory National Centre for Cell Science  Pune 411007 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1040-3631","authenticated-orcid":false,"given":"Mohan R.","family":"Wani","sequence":"additional","affiliation":[{"name":"Bone and Cartilage Research Laboratory National Centre for Cell Science  Pune 411007 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"1","article-title":"Rheumatoid arthritis","volume":"6736","author":"Smolen J. 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