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Cited by 503

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Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis

Open access
He, Helen, Suryawanshi, Hemant, Morozov, Pavel, Gay-Mimbrera, Jesús, Del Duca, Ester, Kim, Hyun Je, Kameyama, Naoya, Estrada, Yeriel, Der, Evan, Krueger, James G., Ruano, Juan, Tuschl, Thomas, Guttman-Yassky, Emma·2020·Journal of Allergy and Clinical Immunology

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 To construct a detailed, high-resolution atlas of cell populations, and to assess variability in cell composition and cell-specific gene expression in the skin of AD patients versus controls METHODS: We performed single-cell RNA-sequencing on skin biopsies from 5 patients with AD (4 lesional samples, 5 non-lesional samples) and 7 healthy control subjects, using 10x Genomics. RESULTS We created transcriptomic profiles for 39,042 AD (lesional and non-lesional) 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. 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 type 1 (IFNG+) in lesional AD, while this ratio was diminished slightly in non-lesional AD and further in controls. CONCLUSION AD lesions were characterized by expanded type 2/type 22 T-cells and inflammatory DCs, and a unique inflammatory fibroblast that may interact with immune cells to regulate lymphoid cell organization and type 2 inflammation.

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Metadata

Authors
He, H., Suryawanshi, H., Morozov, P., Gay-Mimbrera, J., Del Duca, E., Kim, H. J., Kameyama, N., Estrada, Y., Der, E., Krueger, J. G., Ruano, J., Tuschl, T., & Guttman-Yassky, E.
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2020-06
Volume
145
Issue
6
Pages
1615-1628
ISSN
0091-6749 (ISSN-L)
OpenAlex
W3005233576
Cited by
503
References
64
FWCI
39.36
Type
journal article
Language
en
Open access
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He, H., Suryawanshi, H., Morozov, P., Gay-Mimbrera, J., Del Duca, E., Kim, H. J., Kameyama, N., Estrada, Y., Der, E., Krueger, J. G., Ruano, J., Tuschl, T., & Guttman-Yassky, E. (2020). Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2020.01.042

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