Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 145, Issue 6, Pages 1615-1628Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2020.01.042
Keywords
Atopic dermatitis; single-cell RNA sequencing; fibroblasts; dendritic cells; T cells; cytokines
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Funding
- National Center for Advancing Translational Sciences, National Institutes of Health, Clinical and Translational Science Award program [UL1TR001866]
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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.
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