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In situ activation of skin\u2010infiltrating plasmacytoid dendritic cells (pDCs) leading to local induction of type I interferons (IFNs) is a crucial innate initiation event in psoriasis. Psoriatic patients also have notable susceptibility to the development of metabolic syndrome, especially systemic insulin resistance. Interestingly, a crucial role of systemic and metabolic tissue\u2010restricted induction of type I IFNs is now established in metabolic syndrome. We aimed at exploring whether systemic type I IFN abundance contributes to metabolic derangements in psoriatic patients as well. We developed a preclinical murine model of chronic psoriasis that develops systemic insulin resistance, accompanied by a chronic low\u2010grade systemic inflammation. Then we showed that systemic ablation of type I IFN signaling, using a monoclonal antibody against type I IFN receptor IFNAR1, can mitigate the metabolic dysregulation in this preclinical model of psoriasis\u2010associated insulin resistance. Thus, we report a hitherto unknown role of systemic type I IFN abundance in driving systemic insulin resistance and metabolic dysregulations in psoriasis.<\/jats:p>","DOI":"10.1002\/eji.70160","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T06:44:03Z","timestamp":1774853043000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Type I Interferon Blockade Mitigates Insulin Resistance in a Preclinical Model of Psoriasis"],"prefix":"10.1002","volume":"56","author":[{"given":"Bishnu Prasad","family":"Sinha","sequence":"first","affiliation":[{"name":"IICB\u2010Translational Research Unit of Excellence CSIR\u2010Indian Institute of Chemical Biology  Kolkata India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"},{"name":"University of Florida Diabetes Institute University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purbita","family":"Bandopadhyay","sequence":"additional","affiliation":[{"name":"IICB\u2010Translational Research Unit of Excellence CSIR\u2010Indian Institute of Chemical Biology  Kolkata India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md. 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