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Recent studies have demonstrated the therapeutic potential of mesenchymal stem cell\u2010derived extracellular vesicles (MSC\u2010EVs) to psoriasis because of their immunomodulation functions. Yet, the outcome of MSC\u2010EVs alone is still unsatisfactory and the underlying mechanisms are also unclear. Here, it is uncovered that arginase1 (Arg1)\/polyamine is overexpressed in psoriasis patients and murine, inducing the in\u2010situ accumulation of self\u2010antigens. Engineered nor@MSC\u2010EVs are fabricated by loading Arg1 inhibitor nor\u2010NOHA into MSC\u2010EVs for studying the therapeutic effect and mechanism of psoriasis. The nor@MSC\u2010EVs exhibited profound suppression of the NF\u2010\u03baB signaling pathway by targeting Arg1\/polyamine\u2010mediated DCs\/Th17 axis through scavenging self\u2010antigens, resulting in superior mitigation of skin lesions and modulation of local and systemic metabolic and immunological disorders compared to the MSC\u2010EVs and clinically used anti\u2010IL17A both in vitro and in vivo. Together, the results highlight a novel perspective for psoriasis therapy by nor@MSC\u2010EVs with broad clinical translational potential.<\/jats:p>","DOI":"10.1002\/advs.202410067","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T05:55:34Z","timestamp":1733982934000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Engineered Mesenchymal Stem Cell\u2010Derived Extracellular Vesicles Scavenge Self\u2010Antigens for Psoriasis Therapy via Modulating Metabolic and Immunological Disorders"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6090-0460","authenticated-orcid":false,"given":"Xin","family":"Zhou","sequence":"first","affiliation":[{"name":"Research Center The Seventh Affiliated Hospital Sun Yat\u2010sen University  Shenzhen 518107 China"},{"name":"Department of Dermatovenereology The Seventh Affiliated Hospital Sun Yat\u2010sen 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