Single-cell transcriptome sequencing characterizes epithelial, stromal, and immune cell involvement in the IFN-γ–CXCL9/10–CXCR3 axis in vitiligo

Vitiligo is an autoimmune depigmenting disorder characterized by melanocyte loss, yet the cellular landscape underlying the inflammatory networks involved in disease remains incompletely understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on skin samples from patients with non-segmental vitiligo and healthy individuals, including lesional skin (LS, n = 4), paired lesion-adjacent normal skin (LN, n = 4), and healthy control skin (Ctrl, n = 6). Our analysis revealed distinct epithelial, immune, and stromal populations associated with the IFN-γ–CXCL9/10–CXCR3 inflammatory axis in vitiligo. Basal keratinocytes exhibited enhanced CXCL9/CXCL10 expression and an interferon-responsive transcriptional state, as indicated by the expression of interferon receptors and supported at the tissue level by increased IRF1 and phosphorylated STAT1 (p-STAT1) expression. CXCR3 + CD8 + T cells were identified as the major CXCR3-expressing immune population and were validated in vitiligo lesions by immunofluorescence staining. In addition, we identified a JUN-associated endothelial cell (EC) state characterized by an inflammatory transcriptional signature and CXCL9/CXCL10 expression. Together, these findings provide a cellular framework of epithelial, immune, and stromal components associated with the IFN-γ–CXCL9/10–CXCR3 axis and offer insights into the complex inflammatory landscape of vitiligo.