Single cell RNA-seq of psoriatic skin identifies pathogenic Tc17 subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer

Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers. In this study, we used single-cell RNA-seq to identify 11 transcriptionally diverse CD8+ T cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed two Tc17 subsets that were metabolically divergent, developmentally related, and expressed CXCL13, which we found to be a biomarker of psoriasis severity. Despite high co-inhibitory receptor expression in the Tc17 clusters, a comparison of these cells with melanoma-infiltrating CD8+ T cells revealed upregulated cytokine, cytolytic, and metabolic transcriptional activity in the psoriatic cells that differed from an exhaustion program. Our findings provide a high-resolution view of cutaneous CD8+ T cells in psoriasis and healthy skin and shed light on their functional distinctions within the chronic pathologies of autoimmunity and cancer. transcriptomic comparison of CD8+ T cells in 11 psoriatic and 5 healthy skin samples