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However, the mechanism underlying fibrosis remains unclear, and effective treatments for halting or reversing fibrosis are lacking. In this study, single\u2010cell RNA sequencing is used to obtain a comprehensive overview of skin cells from patients with SSc and healthy controls. A subset of basal cells with high chitinase 3\u2010like 1 (Chi3L1) expression, which potentially plays an important role in fibroblast activation, is identified in SSc. Subsequently, patients with SSc are present with increased expression of Chi3L1 in the skin and serum, and elevated serum levels are associated with skin induration and pulmonary function. Furthermore, Chi3L1 promoted the differentiation of SSc dermal fibroblasts into myofibroblasts, and Chi3L1\u2010deficient (Chi3L1\u2010\/\u2010) mice showed amelioration of fibrosis in a bleomycin\u2010induced SSc (BLM\u2010SSc) model. Mechanistically, Chi3L1 mediates fibroblast activation primarily by interacting with interleukin\u201017 receptor A (IL\u201017RA), thereby initiating downstream nuclear factor kappa B and mitogen\u2010activated protein kinases signaling pathways. Moreover, the anti\u2010fibrotic effect of IL\u201017RA antagonists in BLM\u2010SSc mice is demonstrated. In conclusion, Chi3L1 is a potential biomarker for the degree of fibrosis in SSc. Chi3L1 and its receptor, IL\u201017RA, are promising therapeutic targets for patients with SSc.<\/jats:p>","DOI":"10.1002\/advs.202310169","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T03:03:55Z","timestamp":1734404635000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Aberrant Chitinase 3\u2010Like 1 Expression in Basal Cells Contributes to Systemic Sclerosis Fibrosis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7996-6929","authenticated-orcid":false,"given":"Xiuyuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology Zhongshan Hospital of Fudan University  Shanghai 200032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianbao","family":"Ye","sequence":"additional","affiliation":[{"name":"Sixth People's Hospital affiliated to Shanghai Jiao Tong University  Shanghai 200233 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