Single-cell transcriptomics applied to emigrating cells from psoriasis elucidate pathogenic versus regulatory immune cell subsets

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:148

Article

Kim, Jaehwan^1,2  Lee, Jongmi¹  Kim, Hyun Je^3,4,5  Kameyama, Naoya^3,4  Nazarian, Roya²  Der, Evan⁶  Cohen, Steven²  Guttman-Yassky, Emma^3,4  Putterman, Chaim^6,7,8  Krueger, James G.¹ 

[1] Rockefeller Univ, Invest Dermatol Lab, 1230 York Ave, New York, NY 10065 USA

[2] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Dermatol, Bronx, NY 10467 USA

[3] Icahn Sch Med Mt Sinai, Lab Inflammatory Skin Dis, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY 10029 USA

[5] Samsung Med Ctr, Dept Dermatol, Seoul, South Korea

[6] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Rheumatol, Bronx, NY 10467 USA

[7] Azrieli Sch Med, Safed, Ramat Gan, Israel

[8] Galillee Med Ctr, Res Inst, Nahariyya, Israel

关键词: Psoriasis;    single-cell RNA sequencing;    T cells;    dendritic cells;    keratinocytes;    emigrating cells;   

DOI  :  10.1016/j.jaci.2021.04.021

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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