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Liu, Jared; Chang, Hsin-Wen; Huang, Zhi-Ming; Nakamura, Mio; Sekhon, Sahil; Ahn, Richard; Munoz-Sandoval, Priscila; Bhattarai, Shrishti; Beck, Kristen M.; Sanchez, Isabelle M.; Yang, Eric; Pauli, Mariela; Arron, Sarah T.; Fung-Leung, Wai-Ping; Munoz, Ernesto; Liu, Xuejun; Bhutani, Tina; North, Jeffrey; Fourie, Anne M.; Rosenblum, Michael D.; Liao, Wilson
Journal of allergy and clinical immunology, June 2021, 2021-06-00, 20210601, Volume: 147, Issue: 6Journal Article
Psoriasis is an inflammatory, IL-17–driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers. Our study focused on comprehensively characterizing the phenotypic variation of CD8+ T cells in psoriatic lesions. We used single-cell RNA sequencing to compare CD8+ T-cell transcriptomic heterogeneity between psoriatic and healthy skin. We identified 11 transcriptionally diverse CD8+ T-cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed 2 Tc17 cell subsets that were metabolically divergent, were developmentally related, and expressed CXCL13, which we found to be a biomarker of psoriasis severity and which achieved comparable or greater accuracy than IL17A in a support vector machine classifier of psoriasis and healthy transcriptomes. Despite high coinhibitory receptor expression in the Tc17 cell 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. Using high-resolution single-cell profiling in tissue, we have uncovered the diverse landscape of CD8+ T cells in psoriatic and healthy skin, including 2 nonexhausted Tc17 cell subsets associated with disease severity.
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