Epidermal keratinocytes-specific PD-L1 knockout causes delayed healing of diabetic wounds
Zhan Zhang1, Dan Yang2, Fang Shen2
1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Institute of Dermatology, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
Background:
Diabetic ulcers (DUs) is a common complication of diabetes, for which the morbidity and mortality increasing annually worldwide. The deficiency of PD-L1 in keratinocytes (KCs) may be linked to the diabetic wound healing impediments.
Objective:
Our study utilized transgenic mice to assess the functions of epidermal KCs-specific PD-L1 in DUs treatment.
Methods And Results:
Epidermal KCs-specific PD-L1 knockouted mice demonstrate deteriorated healing rates, concomitant with exacerbated inflammatory infiltration and excessive angiogenesis. The streptozotocin-induced murine diabetes model was used to imitate DUs in-vivo context, and the delayed healing was found under diabetic conditions. We then generated transgenic mice overexpressing PD-L1 in the epidermis. PD-L1 overexpression accelerate the DUs healing process accompanied by a reduction in inflammatory infiltration and a corresponding decreasion of angiogenesis. Therefore, overexpression of PD-L1 accelerates the healing process of DUs.
Conclusion:
In sum, epidermal KCs-specific PD-L1 plays vital roles in epidermis regeneration, inflammatory infiltration, and angiogenesis during DUs restoration, and would not be easily to format fibrous scar. Our study elucidated a new therapeutic idea for slow-healing wound care.
