Systemic Type I Interferon Blockade Mitigates Insulin Resistance in a Preclinical Model of Psoriasis.

Abstract

Psoriasis is a cutaneous autoimmune disease with worldwide prevalence. In situ activation of skin-infiltrating 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-restricted 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-grade 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-associated 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.