A distinctive skin gamma delta T cell repertoire in diabetic wound repair 2121

Abstract Description Diabetes Mellitus (DM) is a chronic disorder affecting millions globally, leading to complications like diabetic foot ulcers (DFUs) and impaired wound healing. In the skin, gamma delta T cells (GDTs), a specialized subset of T lymphocytes, regulate inflammation and promote wound repair. We have shown that the expression of the antimicrobial protein, perforin-2 (P-2) in skin GDTs is decreased in DFUs, but the specific roles of GDTs in the DFU microenvironment remain unclear. To investigate, we characterized GDTs in a diabetic mouse model (STZ) and confirmed the role of butyrophilins and butyrophilin-like molecules in their activation. Full-thickness wounds were induced on the dorsal skin of diabetic and nondiabetic three-month-old male and female C57BL/6 and P-2 deficient (-/-) mice, with healing assessed on day 3 post-wounding. Diabetic skin exhibited fewer CD45+CD3+ T cells compared to non-diabetic skin. Circulating Vγ1+ GDTs were significantly higher in diabetic skin, while epidermal Vγ3+ GDTs were significantly lower compared to non-diabetic skin. Wound healing was delayed in diabetic skin, with greater delays in P-2 knockout mice. Co-culture experiments confirmed that epithelial Skint1 induces GDT activation. Our findings underscore the critical role of GDTs in diabetic wound healing, highlight the importance of an intact P-2 GDT cell-mediated response for successful wound closure, and suggest cellular therapeutic targets to improve skin repair. Funding Sources NIH/NINR, R01NR015649-01 NIH/NIDDK, R01DK136241 5T32AI162624-03 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)