1. Single-cell transcriptomics applied to emigrating cells from psoriasis elucidate pathogenic versus regulatory immune cell subsets.
- Author
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Kim, Jaehwan, Lee, Jongmi, Kim, Hyun Je, Kameyama, Naoya, Nazarian, Roya, Der, Evan, Cohen, Steven, Guttman-Yassky, Emma, Putterman, Chaim, and Krueger, James G
- Subjects
Dendritic Cells ,Cells ,Cultured ,Skin ,Humans ,Psoriasis ,Cytokines ,Flow Cytometry ,Cell Separation ,Gene Expression Profiling ,Sequence Analysis ,RNA ,Cell Movement ,Chemokine CCL27 ,Receptors ,CCR10 ,Th17 Cells ,Single-Cell Analysis ,Transcriptome ,T cells ,dendritic cells ,emigrating cells ,keratinocytes ,single-cell RNA sequencing ,Biotechnology ,Genetics ,Autoimmune Disease ,Clinical Research ,1.1 Normal biological development and functioning ,Underpinning research ,Inflammatory and immune system ,Immunology ,Allergy - Abstract
BackgroundIn 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.ObjectiveOur 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.MethodsWe 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.ResultsUnsupervised 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.ConclusionWe 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.
- Published
- 2021