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 expresses CCR6 in response to activation in vitro and post-wounding or psoriasis induction with imiquimod in vivo. We show that CCL20 stimulates epidermal γδ T cells to produce IL-17 suggesting CCR6 regulates the IL-17 axis as in dermal γδ T cells. Further, epidermal γδ T cells upregulate CCR6 and produce IL-17 during murine models of wound repair and psoriasis. Obesity increases CCR6 and IL-17 expression by epidermal γδ T cells during wound repair but has less of an 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.
ABSTRACT
Chronic, nonhealing wounds remain a clinical challenge and a significant burden for the healthcare system. Skin-resident and infiltrating T cells that recognize pathogens, microbiota, or self-antigens participate in wound healing. A precise balance between proinflammatory T cells and regulatory T cells is required for the stages of wound repair to proceed efficiently. When diseases such as diabetes disrupt the skin microenvironment, T cell activation and function are altered, and wound repair is hindered. Recent studies have used cutting-edge technology to further define the cellular makeup of the skin prior to and during tissue repair. In this review, we discuss key advances that highlight mechanisms used by T cell subsets to populate the epidermis and dermis, maintain skin homeostasis, and regulate wound repair. Advances in our understanding of how skin cells communicate in the skin pave the way for therapeutics that modulate regulatory versus effector functions to improve nonhealing wound treatment.
