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Papaverine, an alkaloid with known anti-inflammatory, anti-cancer, and RAGE-antagonistic properties, has not been previously evaluated for anti-psoriatic activity. This study investigated the protective effects and mechanisms of papaverine in an imiquimod (IMQ)\u2013induced psoriasis-like model in BALB\/c mice. Papaverine treatment significantly ameliorated clinical symptoms, as evidenced by reductions in psoriatic lesions, skin thickness, severity index scores, T- and B-cell infiltration, and cutaneous angiogenesis. It also downregulated IMQ-induced mRNA expression of keratinocyte differentiation markers Krt10 and Ivl. Flow cytometric analysis revealed a marked reduction in B220\u207aCD138\u207a plasmablasts and B220\u207bCD138\u207a plasma cells in both circulation and spleen. These effects were associated with modulation of key transcription factors involved in plasma cell differentiation, including Prdm1, Xbp1, and Bcl6. Notably, the population of CD3\u207aCD4\u207bCD8\u207b double-negative T cells was also decreased following papaverine administration. Inflammatory cytokine and chemokine mRNA levels in IMQ-exposed skin\u2014namely Il1b, Il6, Ifng, Mcp1, Il22, S100a7, and Ager\u2014were significantly suppressed. These findings suggest that papaverine ameliorates psoriasis-like symptoms through inhibition of proinflammatory cytokines and suppression of aberrant plasma cell differentiation. In conclusion, papaverine demonstrates therapeutic potential as a candidate for the treatment of psoriasis.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag233","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:59:58Z","timestamp":1789394398000},"source":"Crossref","is-referenced-by-count":0,"title":["Papaverine ameliorates psoriasis-like skin inflammation by regulating immune cell differentiation and RAGE\u2013S100A7 axis in an imiquimod-induced murine model"],"prefix":"10.1093","volume":"215","author":[{"given":"Nontaphat","family":"Leerach","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences , Kanazawa,","place":["Japan"]},{"name":"Princess Srisavangavadhana Faculty of Medicine, Chulabhorn Royal Academy , Bangkok,","place":["Thailand"]},{"name":"Research Center on Clinical and System Microbiology, Chulabhorn Royal Academy , 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