Role of C-C Motif Chemokine Ligand 20 in the Regulation of Epidermal γδ T Cells

Abstract

The epidermis provides a barrier that protects against environmental damage and infection by pathogens. Epidermal T cells and keratinocytes work together to maintain skin homeostasis upon damage. During tissue repair, epidermal γδ T cells become activated to secrete cytokines, chemokines and growth factors to initiate inflammatory responses. Previous work in our lab has shown that during obesity and type 2 diabetes, Chemokine Receptor 6 (CCR6) is downregulated by murine epidermal T cells. The ligand for CCR6, C-C Motif Chemokine Ligand 20 (CCL20), is produced by keratinocytes and is responsible for cellular migration. Little is known about how CCR6 and CCL20 ligation affects epidermal γδ T cells. In this study, murine epidermal γδ T cells were harvested and stimulated in the absence or presence of CCL20 to discover how CCL20 affects activation and function of the cells. Epidermal γδ T cells that have been stimulated with anti-CD3ɛ and CCL20 downregulate their T cell receptor and upregulate CD25 showing cell activation. Interestingly, CCL20 costimulates T cell receptor stimulation to activate epidermal γδ T cells. Immunofluorescent microscopy was used to visualize the impact of CCL20 on activated cells verses non-activated cells in situ. Epidermal γδ T cells treated with CCL20 did not migrate within or out of the epidermis unlike previous studies on dermal γδ T cells. Flow cytometric analysis and Luminex assays were performed to determine which cytokines and chemokines are produced in response to CCL20. We show that CCL20 skews epidermal γδ T cells to produce pro-inflammatory cytokines and chemokines. Future studies will determine how CCL20 and CCR6 ligation affects murine models with obesity and type 2 diabetes.