Exosomes enriched with miR-31-3p from keratinocytes under oxidative stress promote vitiligo progression by destructing melanocytes and activating CD8+ T cells

Vitiligo is a skin disease characterized by the destruction of epidermal melanocytes due to oxidative stress. Keratinocytes are the main responder to oxidative stress and facilitate melanocyte loss by inducing melanocyte death and recruiting antigen-specific CD8⁺ T cell to skin to destroy melanocytes. It has been proved that keratinocytes secrete functional exosomes, but the role of exosomes secreted from keratinocytes under oxidative stress in vitiligo pathogenesis is unknown. The present study investigated the role of exosomes from H₂O₂-treated human keratinocytes in the vitiligo progression in vitro. and in vivo. The results demonstrated that oxidative stress enhanced the secretion of exosomes from keratinocytes. These exosomes (OS-Exos) suppressed the survival of melanocytes while promoting the proliferation and activation of CD8⁺ T cells in vitro. Then, we confirmed that OS-Exos administration aggravated melanocyte loss and CD8⁺ T cell infiltration in the epidermis in the vitiligo mouse model, thereby driving vitiligo progression. Further, we performed Small RNAs-seq to screen miRNAs enriched in OS-Exos. The subsequent results revealed that miR-31-3p, which was enriched in OS-Exos, facilitated melanocyte death and decreased the expression of melanogenesis-related genes through MITF signaling. Meanwhile, it was found that miR-31-3p promoted the activation of CD8⁺ T cells, which could depend on impaired immunosuppression and activated T-cell growth. Taken together, these data suggest that OS-Exos enriched with miR-31-3p facilitated vitiligo progression through the destruction of melanocytes and activation of CD8⁺ T cells. Keratinocytes-derived exosomes under oxidative stress could serve as an important mediator for oxidative stress-induced killing of melanocytes in vitiligo.

CD8(+) T cell; Exosome; Keratinocyte; Melanocyte; Oxidative stress; miRNA.