IL-17A is increased in diabetic wounds and impairs keratinocyte function via histone demethylase JMJD3.

ABSTRACT: IL-17A is a cytokine critical for tissue repair, but in excess, it prolongs inflammation and impairs healing. In type 2 diabetic (T2D) wounds, keratinocyte functions, including migration and inflammation, are disrupted, though mechanisms remain unclear. Here, we demonstrate that IL-17A regulates keratinocyte dysfunction via induction of the histone demethylase Jumonji domain-containing protein 3 (JMJD3) through a TRAF6/NFκB pathway. JMJD3 removes repressive histone 3 lysine 27 (H3K27me3) marks at anti-migratory (Itga3, Timp1) and inflammatory (Ccl20, Cxcl1, Cxcl3, Cxcl5) gene promoters, increasing transcription. Human and murine diabetic wounds exhibit elevated IL-17A signaling, JMJD3, and expression of associated anti-migratory and inflammatory genes compared to controls. Importantly, ker

SUBMITTER: Moon JY 

PROVIDER: S-EPMC12824406 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature