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We previously identified Rh family C glycoprotein (RHCG) as a key mediator of KC inflammation and DC activation. Here, we demonstrate that luteolin, a bioactive compound derived from the traditional Chinese formula cooling blood and detoxicating formula (CBDF), directly binds to RHCG, as confirmed by multiple computational methods and in vitro experiments. In vitro, luteolin suppressed RHCG expression in KCs, reducing CXCL14 secretion and subsequent DC activation. Spatial transcriptomics (STs) revealed that luteolin preferentially targets DC\u2013enriched spatial domains and restores desmosomal protein expression (e.g., DSC2), which is dysregulated in psoriasis. In vivo, luteolin ameliorated psoriasis\u2010like inflammation in imiquimod\u2010induced mice, lowering Psoriasis Area and Severity Index (PASI) scores and normalizing pathological markers. Our findings indicate that luteolin disrupts KC\u2013DC communication through multiple modes of action, thereby reversing tissue\u2010level pathology and demonstrating its potential as a targeted therapy for psoriasis.<\/jats:p>","DOI":"10.1155\/mi\/9564209","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:46:21Z","timestamp":1773301581000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Luteolin Disrupts Keratinocyte\u2013Dendritic Cell Communication in Psoriasis by Targeting Rh Family C 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