Single-cell transcriptomics applied to emigrating cells from psoriasis elucidate pathogenic versus regulatory immune cell subsets - 04/11/21
, Jongmi Lee, MD, PhD a, Hyun Je Kim, MD, PhD c, d, Naoya Kameyama, PhD c, Roya Nazarian, MD b, Evan Der, PhD e, Steven Cohen, MD, MPH b, Emma Guttman-Yassky, MD, PhD c, Chaim Putterman, MD e, f, g, James G. Krueger, MD, PhD a, ⁎ Abstract |
Background |
In previous human skin single-cell data, inflammatory cells 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-γ 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.
Le texte complet de cet article est disponible en PDF.Key words : Psoriasis, single-cell RNA sequencing, T cells, dendritic cells, keratinocytes, emigrating cells
Abbreviations used : AHR, CCL, DC, FLG, KC, MFI, NK, scRNA-seq, T17, Tc17, Treg, Tr1
Plan
| Supported by the National Psoriasis Foundation Discovery Grant 2018 and in part by grant UL1TR001866 from the National Center for Advancing Translational Sciences and the National Institutes of Health Clinical and Translational Science Award program. |
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| Disclosure of potential conflict of interest: J. Kim has received research funds from AbbVie. E. Guttman-Yassky has received research funds from AbbVie, Celgene, Eli Lilly, Janssen, Medimmune/AstraZeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and UCB, and he is also a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. J. G. Krueger has received research support from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 148 - N° 5
P. 1281-1292 - novembre 2021 Retour au numéro
Article précédent
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