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However, the role of C3aR in psoriasis remains unknown. The purpose of this study was to investigate the possible protective role of C3aR in psoriasis and to explore the underlying molecular mechanisms. We initially found that the psoriatic epidermis exhibited significantly decreased C3aR expression. C3aR showed protective roles in mouse models of imiquimod (IMQ)\u2010 and interleukin\u201023\u2010induced psoriasis. Furthermore, increased epidermal thickness and keratin 6 (K6), K16, and K17 expression occurred in the ears and backs of C3aR\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Pharmacological treatment with a C3aR agonist ameliorated IMQ\u2010induced psoriasiform lesions in mice and decreased the expression of K6, K16, and K17. Additionally, the signal transducer and activator of transcription 3 (STAT3) pathway participated in the protective function of C3aR. More importantly, the expression levels of K6, K16, and K17 in keratinocytes were all restored in HaCaT cells transfected with a C3aR\u2010overexpression plasmid after treating them with colivelin (a STAT3 activator). Our findings demonstrate that C3aR protects against the development of psoriasis and suggest that C3aR confers protection by negatively regulating K6, K16, and K17 expression in a STAT3\u2010dependent manner, thus inhibiting keratinocyte proliferation and helping reverse the pathogenesis of psoriasis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202101458r","type":"journal-article","created":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T02:51:16Z","timestamp":1650077476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Activation of the C3a anaphylatoxin receptor inhibits keratinocyte proliferation by regulating keratin 6, keratin 16, and keratin 17 in psoriasis"],"prefix":"10.1096","volume":"36","author":[{"given":"Pei","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Dermatology Xijing Hospital Fourth Military Medical University  Xi'an China"},{"name":"Department of 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