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Deucravacitinib (Deu), a selective oral Tyrosine Kinase 2 (TYK2) inhibitor, shows promise in treating psoriasis but may cause systemic side effects and fail to address persistent localized thickened lesions. Herein, a self\u2010locking microneedle (MN) patch with a polyvinyl alcohol (PVA) inner ring loaded with Deu is developed, designed to penetrate the transdermal barriers and dissolve rapidly, downregulating the IL\u201023\/IL\u201017 pathway and serve as the first line of defense against the spread of skin\u2010originated inflammation. Additionally, Calcipotriol (Cal), a vitamin D derivative, is incorporated into a methacrylated hyaluronic acid (HAMA) backing layer and outer ring that mimics occlusive administration, maintaining localized skin surface retention for prolonged anti\u2010proliferative therapy. The Deu@Cal MN demonstrates satisfactory adhesiveness due to swelling\u2010mediated mechanical interlocking via the outer ring, ensuring targeted drug release at lesion site. Besides its effectiveness in alleviating both skin inflammation and proliferation, it inhibits the differentiation of Th17 cells in the spleen, suggesting potential to reduce systemic inflammation. These findings offer a new therapeutic approach for treating psoriasis and other autoimmune and inflammatory conditions.<\/jats:p>","DOI":"10.1002\/advs.202409359","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T09:11:40Z","timestamp":1730279500000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Dual\u2010Action Psoriasis Therapy: Antiproliferative and Immunomodulatory Effects via Self\u2010Locking Microneedles"],"prefix":"10.1002","volume":"11","author":[{"given":"Zi Yi","family":"Wang","sequence":"first","affiliation":[{"name":"China\u2010Japan Friendship Hospital (Institute of Clinical Medical Sciences) Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing 100029 China"},{"name":"Department of Dermatology China\u2010Japan Friendship Hospital  Beijing 100029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze 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