Ahmed, J.; Matthews, C.; Tulloch, P.; Lawler, W.; Mendoza, A.; Rhoiney, M.; Jameson, J.

Psoriasis is a chronic skin disease that results in scaly patches and affects 2-3% of people worldwide. Therapeutic treatment targets the TNF-/IL-17 axis to disrupt keratinocyte hyperproliferation and inflammation. While more is known about the role of dermal {beta} and {gamma}{delta} T cells in IL-17 production, less is understood about the role of resident epidermal T cells. Here, we examine how TNF- modulates epidermal {gamma}{delta} T cell activation and function. We show that a subset of activated epidermal {gamma}{delta} T cells expresses TNFR2 with or without TNFR1. Stimulation with TNF- induces epidermal {gamma}{delta} T cells to produce IL-17 family cytokines and chemokines. Epidermal {gamma}{delta} T cells do not require TNFR1 or 2 for development or homing to the skin. Instead, TNFR2 plays roles in epidermal {gamma}{delta} T cell function skewing them toward a TJG17 phenotype during psoriasis. Investigation of the mechanisms by which TNF- associated inflammation impacts epidermal {gamma}{delta} T cell function may help identify new cellular targets for immunotherapy or mark them as early regulators of skin inflammation.