Defects in dermal V gamma 4 gamma delta T cells result in delayed wound healing in diabetic mice

The skin serves as a physical and chemical barrier to provide an initial line of defense against environmental threats; however, this function is impaired in diabetes. V gamma 4 gamma delta T cells in the dermis are an important part of the resident cutaneous immunosurveillance program, but these cells have yet to be explored in the context of diabetes. In this study, we observed that the impaired maintenance of dermal V gamma 4 gamma delta T cells is caused by reduced production of IL-7 in the skin of diabetic mice, which was closely associated with weakened activation of the mTOR pathway in the epidermis of diabetic mice. Weakened CCL20/CCR6 chemokine signaling resulted in the impaired recruitment of dermal V gamma 4 gamma delta T cells following wounding in diabetic mice. Meanwhile, reduced levels of IL-23 and IL-1 beta in the dermis around the wounds of diabetic mice resulted in the impaired production of IL-17 by dermal V gamma 4 gamma delta T cells. Therefore, diminished dermal V gamma 4 gamma delta T cells and impaired IL-17 production by these cells were important factors in the markedly reduced IL-17 levels in the skin around the wounds of diabetic mice. Because reduced IL-17 levels at the wound edge have been closely associated with delayed wound closure in diabetic mice, defects in dermal V gamma 4 gamma delta T cells may be an important mechanism underlying delayed wound healing in diabetic mice.