DCUN1D1, a new molecule involved in depigmentation via upregulating CXCL10

CD8⁺ T cells in the lesioned site play a crucial role in the pathogenesis of vitiligo. The chemokine CXCL10 secreted by keratinocytes regulates the migration of CD8⁺ T cells into the skin. In our previous study, we found that DCUN1D1 expression in vitiligo lesions positively correlates with Cxcl10 expression. In this study, the regulatory effect of DCUN1D1 on CXCL10 and cell function was investigated. DCUN1D1 protein expression was significantly higher in the skin tissue from vitiligo lesions compared with samples from healthy controls. High expression of DCUN1D1 in keratinocytes caused local hair depigmentation in mice, reduced melanin content, high infiltration of CD8⁺ T cells and increased CXCL10 expression. This suggested that DCUN1D1 may regulate CD8⁺ T-cell infiltration and depigmentation through CXCL10. Inhibition of DCUN1D1 expression in HaCaT cells abolished the IFN-γ-induced upregulation of p-JAK1, p-STAT1 and CXCL10, suppressed the H₂ O₂ -induced ROS generation and apoptosis, and upregulated tyrosinase expression in melanocytes. Collectively, these results show that DCUN1D1 is an important regulator of CXCL10 and may be a new target for the treatment of vitiligo.