Spatial transcriptomic analysis of the immune landscape following <scp>NBUVB</scp> treatment of vitiligo skin

Abstract Objectives Vitiligo is an autoimmune disorder characterised by the presence of depigmented lesions on the skin. The autoreactive cytotoxic T cells at the epidermal‐dermal junction of the skin facilitate the targeted destruction of epidermal melanocytes, leading to the development of vitiligo lesions. Narrow‐band UVB (NBUVB) phototherapy is a widely used non‐invasive treatment that promotes transient repigmentation of lesions. However, the specific effects of NBUVB on skin dermal T cells in vitiligo patients remain largely unexplored. Insights into the mechanism of action of NBUVB phototherapy can guide therapies against cytotoxic T cells, enabling effective and sustained remission of vitiligo lesions. Methods Indian patients with active vitiligo lesions underwent 3 months of NBUVB phototherapy, thereby leading to successful repigmentation of vitiligo lesions. Spatial transcriptomic and histological analyses were employed to investigate the gene expression profiles of dermal T cells at the epidermal‐dermal junction, both before and after treatment. Results Comprehensive spatial transcriptome analysis of skin dermal T cells revealed that NBUVB phototherapy leads to the overall suppression of inflammatory genes and immune regulatory pathways that are upregulated in vitiligo patients before treatment. Consequently, tissue‐resident innate and adaptive immune cells significantly decrease post‐UVB phototherapy. Interestingly, we observe an increase in naïve CD4 + T cells post‐UVB phototherapy. Conclusion NBUVB phototherapy effectively suppresses the innate and adaptive immune cell populations and immune regulatory pathways while promoting an increase in naïve CD4 + T cells. These findings underscore a previously unrecognised immunomodulatory role of NBUVB phototherapy in vitiligo patients.