期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 148, 期 5, 页码 1281-1292出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2021.04.021
关键词
Psoriasis; single-cell RNA sequencing; T cells; dendritic cells; keratinocytes; emigrating cells
资金
- National Psoriasis Foundation
- National Center for Advancing Translational Sciences [UL1TR001866]
- National Institutes of Health Clinical and Translational Science Award program
This study utilized single-cell transcriptomics to analyze emigrating cells from the skin, revealing gene expression profiles of pathogenic and regulatory immune cell subsets in individuals with psoriasis. The findings also highlighted differences in key signaling pathways in psoriasis.
Background: In previous human skin single-cell data, inflammatorycells constituted only a small fraction of the overall cell population, such that functional subsets were difficult to ascertain. Objective: Our aims were to overcome the aforesaid limitation by applying single-cell transcriptomics to emigrating cells from skin and elucidate ex vivo gene expression profiles of pathogenic versus regulatory immune cell subsets in the skin of individuals with psoriasis. Methods: We harvested emigrating cells from human psoriasis skin after incubation in culture medium without enzyme digestion or cell sorting and analyzed cells with single-cell RNA sequencing and flow cytometry simultaneously. Results: Unsupervised clustering of harvested cells from psoriasis skin and control skin identified natural killer cells, T-cell subsets, dendritic cell subsets, melanocytes, and keratinocytes in different layers. Comparison between psoriasis cells and control cells within each cluster revealed that (1) cutaneous type 17 T cells display highly differing transcriptome profiles depending on IL-17A versus IL-17F expression and IFN-gamma versus IL-10 expression; (2) semimature dendritic cells are regulatory dendritic cells with high IL-10 expression, but a subset of semimature dendritic cells expresses IL-23A and IL-36G in psoriasis; and (3) CCL27-CCR10 interaction is potentially impaired in psoriasis because of decreased CCL27 expression in basal keratinocytes. Conclusion: We propose that single-cell transcriptomics applied to emigrating cells from human skin provides an innovative study platform to compare gene expression profiles of heterogenous immune cells in various inflammatory skin diseases.
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