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Keratinocytes, the primary cells in epidermis, play a pivotal role in orchestrating the UV\u2010induced immunosuppressive response by releasing platelet\u2010activating factor (PAF) upon UV exposure. Adopting a paradigm shift that transforms a known health hazard as a potential therapeutic asset, a novel therapeutic strategy is set out to investigate for inflammatory conditions by leveraging immunosuppressive properties of UV\u2010irradiated keratinocytes. To safely exploit this mechanism, extracellular vesicles are isolated from UV\u2010irradiated keratinocytes, designate\n                    <jats:sup>UV<\/jats:sup>\n                    KEV, and assess their potential as immunomodulatory agents in the mouse model of inflammatory bowel disease (IBD) and imiquimod (IMQ)\u2010induced psoriasis. Subcutaneous administration of\n                    <jats:sup>UV<\/jats:sup>\n                    KEV efficiently stimulates the secretion of prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ) by keratinocytes and promotes the migration of mast cells to lymph nodes through the PAF\/PAF receptor pathway. The as\u2010prepared\n                    <jats:sup>UV<\/jats:sup>\n                    KEV effectively reshapes the immune landscape within the spleen by inhibiting dendritic cell maturation and increasing the population of regulatory T cells. Animal studies confirm that\n                    <jats:sup>UV<\/jats:sup>\n                    KEV can result in robust systemic immune tolerance and significantly alleviate the symptoms of both IBD and psoriasis. This study presents the possibility of\n                    <jats:sup>UV<\/jats:sup>\n                    KEV as natural immunoregulatory therapeutics for the managing inflammatory disorders with promising clinical potential.\n                  <\/jats:p>","DOI":"10.1002\/advs.202501517","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T02:59:52Z","timestamp":1751511592000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Harnessing the Immunomodulation of UV\u2010Exposed Keratinocyte Extracellular Vesicles for Inflammatory Disorder Treatment"],"prefix":"10.1002","volume":"12","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology Department of Pharmacology and Pharmacy and Dr. Li Dak\u2010Sum Research Centre The University of Hong Kong  Hong Kong 999077 China"},{"name":"Department of Minimally 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