Using a series of in vivo studies with a geneticall y engineered mouse model (Mll1fl/flK14cre–) and human wound tissues from patients with T2D, we demonstrate that MLL1 controls wound keratinocyte–mediated Ifnk expression and that Mll1 expression is decreased in T2D keratinocytes. Here, IFNK is linked to type 2 diabetes mellitus.