Vγ4 T Cells Inhibit the Pro-healing Functions of Dendritic Epidermal T Cells to Delay Skin Wound Closure Through IL-17A.

Dendritic epidermal T cells (DETCs) and dermal V gamma 4 T cells engage in wound re-epithelialization and skin inflammation. However, it remains unknown whether a functional link between V gamma 4 T cell pro-inflammation and DETC pro-healing exists to affect the outcome of skin wound closure. Here, we revealed that V gamma 4 T cell-derived IL-17A inhibited IGF-1 production by DETCs to delay skin wound healing. Epidermal IL-1 beta and IL-23 were required for V gamma 4 T cells to suppress IGF-1 production by DETCs after skin injury. Moreover, we clarified that IL-1 beta rather than IL-23 played a more important role in inhibiting IGF-1 production by DETCs in an NF-kappa B-dependent manner. Together, these findings suggested a mechanistic link between V gamma 4 T cell-derived IL-17A, epidermal IL-1 beta/IL-23, DETC-derived IGF-1, and wound-healing responses in the skin.