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Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer
- 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
- et al.
Published Web Location
https://doi.org/10.1016/j.jaci.2020.11.028Abstract
Background
Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers.Objective
Our study focused on comprehensively characterizing the phenotypic variation of CD8+ T cells in psoriatic lesions.Methods
We used single-cell RNA sequencing to compare CD8+ T-cell transcriptomic heterogeneity between psoriatic and healthy skin.Results
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.Conclusion
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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