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Despite extensive research, the precise mechanisms underlying psoriasis pathology and treatment strategies remain unclear because of a complex aetiology and disease progression. Hence, in this study, we aimed to identify potential therapeutic targets for psoriasis and explore their effects on disease progression. We observed that G protein\u2010coupled receptor LGR4 attenuates psoriasis progression. Bioinformatics analysis of publicly available clinical data revealed lower LGR4 expression in the skin lesions of patients with psoriasis than in their non\u2010lesioned skin. Both in\u00a0vitro (HaCaT cell) and in\u00a0vivo (mouse) models confirmed this phenomenon. The <jats:italic>Lgr4<\/jats:italic>\u2010knockout mouse model further confirmed that LGR4 plays a positive role in psoriasis progression. Specifically, <jats:italic>Lgr4<\/jats:italic> knockout promoted the secretion of inflammatory factors, accumulation of local immunocyte infiltration in skin lesions, and keratinocyte proliferation. In conclusion, we demonstrated that LGR4 is critical to limiting psoriasis progression, suggesting that it is a viable target for the clinical management of this skin condition.<\/jats:p>","DOI":"10.1111\/imm.13873","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T08:10:01Z","timestamp":1732090201000},"page":"213-225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>LGR4<\/scp> Deficiency Aggravates Skin Inflammation and Epidermal Hyperplasia in Imiquimod\u2010Induced Psoriasis"],"prefix":"10.1111","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6203-1860","authenticated-orcid":false,"given":"Mengfei","family":"Xue","sequence":"first","affiliation":[{"name":"Shanghai Fengxian District Central Hospital, School of Medicine Anhui University of Science and Technology  Shanghai 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