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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.
- Source :
-
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2021 Jun; Vol. 147 (6), pp. 2370-2380. Date of Electronic Publication: 2020 Dec 09. - Publication Year :
- 2021
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Abstract
- Background: Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8 <superscript>+</superscript> T cells have been identified as pathogenic drivers.<br />Objective: Our study focused on comprehensively characterizing the phenotypic variation of CD8 <superscript>+</superscript> T cells in psoriatic lesions.<br />Methods: We used single-cell RNA sequencing to compare CD8 <superscript>+</superscript> T-cell transcriptomic heterogeneity between psoriatic and healthy skin.<br />Results: We identified 11 transcriptionally diverse CD8 <superscript>+</superscript> 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 <superscript>+</superscript> T cells revealed upregulated cytokine, cytolytic, and metabolic transcriptional activity in the psoriatic cells that differed from an exhaustion program.<br />Conclusion: Using high-resolution single-cell profiling in tissue, we have uncovered the diverse landscape of CD8 <superscript>+</superscript> T cells in psoriatic and healthy skin, including 2 nonexhausted Tc17 cell subsets associated with disease severity.<br /> (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Case-Control Studies
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
Humans
Immunologic Memory
Immunophenotyping
Interleukin-17 biosynthesis
Neoplasms genetics
Neoplasms immunology
Single-Cell Analysis
Autoimmunity
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Psoriasis etiology
Psoriasis metabolism
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6825
- Volume :
- 147
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of allergy and clinical immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33309739
- Full Text :
- https://doi.org/10.1016/j.jaci.2020.11.028