Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis - 08/06/20
, Pavel Morozov, PhD b, Jesús Gay-Mimbrera, PhD c, Ester Del Duca, MD a, Hyun Je Kim, MD, PhD a, Naoya Kameyama, PhD a, Yeriel Estrada, BS a, Evan Der, BS d, James G. Krueger, MD, PhD e, Juan Ruano, MD, PhD c, Thomas Tuschl, PhD b, ⁎ , Emma Guttman-Yassky, MD, PhD a, ⁎ Abstract |
Background |
Atopic dermatitis (AD) is a prevalent inflammatory skin disease with a complex pathogenesis involving immune cell and epidermal abnormalities. Despite whole tissue biopsy studies that have advanced the mechanistic understanding of AD, single cell–based molecular alterations are largely unknown.
Objective |
Our aims were to construct a detailed, high-resolution atlas of cell populations and assess variability in cell composition and cell-specific gene expression in the skin of patients with AD versus in controls.
Methods |
We performed single-cell RNA sequencing on skin biopsy specimens from 5 patients with AD (4 lesional samples and 5 nonlesional samples) and 7 healthy control subjects, using 10× Genomics.
Results |
We created transcriptomic profiles for 39,042 AD (lesional and nonlesional) and healthy skin cells. Fibroblasts demonstrated a novel COL6A5+COL18A1+ subpopulation that was unique to lesional AD and expressed CCL2 and CCL19 cytokines. A corresponding LAMP3+ dendritic cell (DC) population that expressed the CCL19 receptor CCR7 was also unique to AD lesions, illustrating a potential role for fibroblast signaling to immune cells. The lesional AD samples were characterized by expansion of inflammatory DCs (CD1A+FCER1A+) and tissue-resident memory T cells (CD69+CD103+). The frequencies of type 2 (IL13+)/type 22 (IL22+) T cells were higher than those of type 1 (IFNG+) in lesional AD, whereas this ratio was slightly diminished in nonlesional AD and further diminished in controls.
Conclusion |
AD lesions were characterized by expanded type 2/type 22 T cells and inflammatory DCs, and by a unique inflammatory fibroblast that may interact with immune cells to regulate lymphoid cell organization and type 2 inflammation.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Atopic dermatitis, single-cell RNA sequencing, fibroblasts, dendritic cells, T cells, cytokines
Abbreviations used : AD, CCL, cDC, cDC1, cDC2, CXCL, DC, DEG, ECM, FB1, FB2, FB3, IRS, KC1, KC2, KC3, LC, LEC, NC, POSTN, SC, scRNA-seq, SGC, TEWL, TPM, TRM, VEC, vSMC
Plan
| Disclosure of potential conflict of interest: J. G. Krueger is an employee of Rockefeller University and has received research support (grants paid to his institution) and/or personal fees from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. E. Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to her institution) from AbbVie, Celgene, Eli Lilly, Janssen, Medimmune/Astra Zeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and UCB and 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. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 145 - N° 6
P. 1615-1628 - juin 2020 Retour au numéro
Article précédent
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