Keratinocyte-derived Exosomal LKB1 Drives Vitiligo Progression by Activating CD8

Keratinocytes are increasingly recognized as active regulators of immune activation and tissue-specific recruitment of CD8⁺ T cells in vitiligo. While keratinocyte-derived exosomes have been implicated in disease pathogenesis, their role in modulating CD8⁺ T cell–mediated cytotoxicity against melanocytes remains unclear. In this study, we successfully isolated exosomes (Vexo) from primary keratinocytes of vitiligo lesional skin and demonstrated their ability to significantly activate CD8⁺ T cells, thereby promoting disease progression. Further analysis revealed a specific enrichment of liver kinase B1 (LKB1) within Vexo, along with its elevated expression in vitiligo patient skin compared to normal controls. Mechanistically, Vexo facilitates the transfer of LKB1 into CD8⁺ T cells and activates them via the LKB1/AMPK signaling pathway. Notably, Vexo-activated CD8⁺ T cells secrete IFN-γ, which in turn induces LKB1 transcription in keratinocytes through STAT1 signaling, establishing a positive feedback loop that amplifies immune activation and exacerbates vitiligo pathogenesis. Together, our results identify keratinocyte-derived exosomal LKB1 as a critical driver of CD8⁺ T cell activation and vitiligo progression, unveiling a pathogenic keratinocyte–T cell feedback circuit and nominating LKB1 as a potential therapeutic target for vitiligo intervention.