122 Normalization of CD8+ T cell metabolism inhibits and reverses depigmentation in vitiligo

Vitiligo is a depigmentation skin disorder mediated by autoreactive CD8+ T cells and estimated to affect 0.5-2% of the general population. Owing to the limitation of existing treatments, safe and affordable treatments are urgently needed. The regulation of T cell activation and function by cellular metabolism has been demonstrated. Nevertheless, the metabolic status of autoimmune CD8+ T cells in vitiligo remains unclear. We found abnormally increased oxidative phosphorylation (OXPHOS) and glycolysis of peripheral blood CD8+ T cells in vitiligo patients. Using metformin (Met) and 2-deoxyglucose (2DG), the classical metabolic regulators, the levels of IFN-γ secreted by CD8+ T cells were significantly reduced. Furthermore, we constructed a vitiligo mouse model based on autoreactive CD8+ T cells and found a hypermetabolic state of spleen CD8+ T cells using live cell real-time metabolic assay (seahorse). Initial administration of Met and 2DG normalized the abnormal metabolism of CD8+ T cells in vitiligo mice and significantly reduced the degree of depigmentation, or even eliminated obvious depigmentation. In the late stage, vitiligo mice receiving Met and 2DG treatment developed repigmentation, with reduced levels of CD8+ T cell infiltration. Our study demonstrated that high glycolysis and mitochondrial oxidative metabolism in CD8+T cells contribute to vitiligo pathogenesis. Moreover, the normalization of their metabolism through the dual inhibition of glycolysis and mitochondrial metabolism not only inhibits disease progression, but also induces repigmentation of vitiligo.