Vitiligo is an inflammatory disease that presents as well-demarcated, depigmented skin lesions. While different mechanisms are implicated in the development and maintenance of vitiligo lesions, immune-mediated destruction of melanocytes has been ascribed the major mechanism of depigmentation. We have previously observed enrichment of cytotoxic resident CD49a+ CD103+ T-cells in the skin of vitiligo patients and recent single cell data highlights crosstalk between CD8+ effector and Treg cells within the lesion, as well as a subclinical state of activation in the non-lesional skin. Here, T cell composition and how these cells interact in situ with melanocytes was assessed in lesional, peri-lesional, and non-lesional skin with Nanostring GeoMX spatial proteomics and 10x Genomics Visium spatial transcriptomic systems. We observed increased levels of S100B protein in the T cell and melanocyte colocalisations in vitiligo skin, previously proposed as a marker for disease activity. Spatial transcriptomic analysis corroborated these finding by revealing increased expression of S100 family genes in the basal epidermal layer of vitiligo lesion, combined with decreased expression of several collagen related genes. Pan- T cell activation in vitiligo skin activated IFNg pathway related genes and genes responsible for proteasome assembly proteins. While some of the genes were also upregulated in activated non-lesional and healthy skin, the levels of expression were several-fold higher in lesional vitiligo. Overall our study shows that the vitiligo skin is a site of quiet inflammation and melanocyte injury, with quiescent IFNg dominated pathophysiology that is induced following T cell activation.

ESDR522 - T cell tissue responses and spatial profiling of vitiligo skin

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.