Pemphigus vulgaris (PV) is an autoimmune blistering disease, in which autoantibodies against desmogleins (Dsg) 1 and Dsg3 interfere with epidermal cell-cell adhesion, thereby causing blister formation and erosions of the skin and/or mucous membranes. Autoreactive Dsg-specific T cells play a central role in the PV pathogenesis. However, little is known about T cells in PV skin lesions and a detailed phenotypical and functional analysis is currently missing. Therefore, we aimed to comprehensively characterize T cells residing in lesional and perilesional skin of PV patients as well as matched peripheral blood compared to healthy controls. Skin biopsies were enzymatically digested followed by phenotypic analysis using multicolour flow cytometry. Preliminary results suggested a predominance of CD4+ T cells as well as an enrichment of regulatory T cells in the skin of PV patients compared to healthy controls. Investigating the permanent residence of these cells, we found all tissue-residency markers to be expressed on T cells in skin. However, the expression of such markers, particularly CD69, was diminished in T cells from PV lesions, suggesting an impact of inflammation and epithelial layer destruction on T cell immunity. Furthermore, tissue-resident T cells exhibited a chemokine receptor profile known for skin-homing. Future experiments will shed more light on the T cell phenotype and functionality in these tissues. In conclusion, this study contributes to a comprehensive characterization of T cells in affected skin of PV patients, which is of particular interest for disease monitoring as well as for the identification of potential therapeutic targets.

ESDR011 - Investigating the role of skin-resident T cells in pemphigus vulgaris in humans

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING