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

卷:145

Article

He, Helen¹  Suryawanshi, Hemant²  Morozov, Pavel²  Gay-Mimbrera, Jesus⁴  Del Duca, Ester¹  Kim, Hyun Je¹  Kameyama, Naoya¹  Estrada, Yeriel¹  Der, Evan^5,6  Krueger, James G.³  Ruano, Juan⁴  Tuschl, Thomas²  Guttman-Yassky, Emma¹ 

[1] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY 10029 USA

[2] Rockefeller Univ, Lab RNA Mol Biol, 1230 York Ave, New York, NY 10065 USA

[3] Rockefeller Univ, Lab Invest Dermatol, New York, NY 10065 USA

[4] Reina Sofia Univ Hosp, Dept Dermatol, Cordoba, Spain

[5] Albert Einstein Coll Med, Div Rheumatol, New York, NY USA

[6] Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY USA

关键词: Atopic dermatitis;    single-cell RNA sequencing;    fibroblasts;    dendritic cells;    T cells;    cytokines;   

DOI  :  10.1016/j.jaci.2020.01.042

来源: Elsevier

【 摘 要 】

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 10x 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 (IL1(3+))/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.

【 授权许可】

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