HMGB1-mediated chromatin remodeling attenuates Il24 gene expression for the protection from allergic contact dermatitis

Abstract

Significance High-mobility group box 1 protein (HMGB1) protein gained attention for its proinflammatory function in a number of pathological conditions, such as skin inflammation. In this study, a Cre/loxP-engineered mouse strain allowed for HMGB1 conditionally ablated in keratinocytes. When allergic contact dermatitis was induced in the HMGB1 mutant mice, skin inflammation was exacerbated in the mutant mice. Expression of interleukin-24 (IL-24), a proinflammatory cytokine associated to skin inflammatory disorders, was elevated in skin lesions of these mice. We also adduced evidence that that HMGB1 represses the binding of histone H3 (lys4) (H3K4me3) to the Il24 gene promoter in keratinocytes. Therefore, our study revealed a facet of nuclear HMGB1 that represses the Il24 gene for the suppression of allergic inflammatory skin disorders.