High-dose NB-UVB exacerbates vitiligo progression by inducing dermal fibroblast senescence through the p38 MAPK signaling pathway.

Vitiligo is an acquired and polygenetic autoimmune disorder with limited effective treatments. Dermal fibroblasts play a key role in vitiligo by responding to IFN-γ and secreting chemokines to recruit and activate CD8+ T cells. Although narrowband UVB (NB-UVB) is a common treatment for vitiligo, it can cause side effects such as phototoxicity. This study investigated the relationship between NB-UVB and fibroblast senescence in vitiligo and the mechanisms through which NB-UVB may trigger disease progression in some cases of vitiligo. Analysis of publicly available single-cell and bulk RNA-sequencing data revealed that NB-UVB irradiation induces dermal fibroblast senescence and activates both the MAPK and p53 pathways. In vitro, high-dose NB-UVB exposure leads to increased senescence and inflammation in vitiligo fibroblasts. In mice with vitiligo, low-dose NB-UVB treatment significantly reduced the number of CD8+ T cells and increased skin pigmentation. In contrast, high-dose NB-UVB induces a senescent, proinflammatory microenvironment and exacerbates vitiligo progression in some cases. In mouse skin, high-dose NB-UVB treatment induces cell senescence and the expression of chemokines and cytokines increases, thereby disrupting the skin microenvironment and homeostasis.