1,25-Dihydroxyvitamin D₃ Provides Benefits in Vitiligo Based on Modulation of CD8+T Cell Glycolysis and Function

Vitiligo is a common autoimmune skin disease caused by autoreactive CD8+ T cells. The diverse effects of 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D-3] on immune cell metabolism and proliferation have made it an interesting candidate as a supporting therapeutic option in various autoimmune diseases. This study aimed to elucidate the immunomodulatory effects of 1,25(OH)(2)D-3 in vitiligo. Cross-sectional relationships between serum 1,25(OH)(2)D-3 levels and disease characteristics were investigated in 327 patients with vitiligo. The immunomodulatory and therapeutic effects of 1,25(OH)(2)D-3 were then investigated in vivo and in vitro, respectively. We found that 1,25(OH)(2)D-3 deficiency was associated with hyperactivity of CD8+ T cells in the vitiligo cohort. In addition, 1,25(OH)(2)D-3 suppressed glycolysis by activating the AMP-activated protein kinase (AMPK) signaling pathway, thereby inhibiting the proliferation, cytotoxicity and aberrant activation of CD8+ T cells. Finally, the in vivo administration of 1,25(OH)(2)D-3 to melanocyte-associated vitiligo (MAV) mice reduced the infiltration and function of CD8+ T cells and promoted repigmentation. In conclusion, 1,25(OH)(2)D-3 may serve as an essential biomarker of the progression and severity of vitiligo. The modulation of autoreactive CD8+ T cell function and glycolysis by 1,25(OH)(2)D-3 may be a novel approach for treating vitiligo.