Jaehwan Kim1, Jongmi Lee2, Hyun Je Kim3, Naoya Kameyama4, Roya Nazarian5, Evan Der6, Steven Cohen5, Emma Guttman-Yassky4, Chaim Putterman7, James G Krueger8. 1. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Medicine, Division of Dermatology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY. Electronic address: jkim05@rockefeller.edu. 2. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY. 3. Department of Dermatology, and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Dermatology, Samsung Medical Center, Seoul, Korea. 4. Department of Dermatology, and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. 5. Department of Medicine, Division of Dermatology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY. 6. Department of Medicine, Division of Rheumatology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY. 7. Department of Medicine, Division of Rheumatology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Azrieli School of Medicine, Safed, Israel; Research Institute, Galillee Medical Center, Nahariya, Israel. 8. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY. Electronic address: kruegej@mail.rockefeller.edu.
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.
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.
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