Impact of obesity on the CCR6-CCL20 axis in epidermal γδ T cells and IL-17A production in murine wound healing and psoriasis.

Abstract

Obesity is associated with comorbidities including type 2 diabetes, chronic nonhealing wounds, and psoriasis. Normally, skin homeostasis and repair is regulated through the production of cytokines and growth factors derived from skin-resident cells including epidermal γδ T cells. However, epidermal γδ T cells exhibit reduced proliferation and defective growth factor and cytokine production during obesity and type 2 diabetes. One of the genes modulated in epidermal γδ T cells during obesity and type 2 diabetes is CCR6, which is the receptor for CCL20. CCL20 is elevated in the skin during obesity and type 2 diabetes. Here, we identify a subset of murine epidermal γδ T cells that express CCR6 upon activation, both in vitro and in vivo. We show that CCL20 stimulates epidermal γδ T cells to produce interleukin (IL)-17, indicating that CCR6 regulates the IL-17 axis in epidermal γδ T cells. In murine models of wound repair and psoriasis, these epidermal γδ T cells upregulate CCR6 and produce IL-17, with obesity amplifying this response during wound repair but having less effect during psoriasis. These findings have novel implications for the regulation of a specific population of IL-17-producing epidermal γδ T cells during skin damage and inflammation.