Loss of epidermal p38α signaling prevents ultraviolet radiation-induced inflammation via acute and chronic mechanisms

Abstract

Ultraviolet B radiation (UVB) is a component of solar radiation primarily responsible for causing damage and cancer in irradiated skin, and disrupting immune homeostasis. The immediate harm and long-term health risks of excessive sunlight exposure are impacting the lives of nearly all people worldwide. Inflammation is a key mechanism underlying UVB’s various detrimental effects. Here we show that activation of the protein kinase p38α is restricted to the epidermis in UVB-exposed skin, and p38α ablation targeted to the epithelial compartment is sufficient to suppress UVB-induced inflammation. Mechanistically, loss of epithelial p38α signaling attenuates the expression of genes required to induce vascular leakage and edema, and also increases the steady-state abundance of epidermal γδ T cells, which are known to promote the repair of damaged epidermis. These effects of p38α deficiency delineate a molecular network operating at the organism-environment interface, and reveal conditions crucial to preventing the pathology resulting from sun-damaged skin.