RT Journal Article
T1 Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis.
A1 He, Helen
A1 Suryawanshi, Hemant
A1 Morozov, Pavel
A1 Gay-Mimbrera, Jesús
A1 Del Duca, Ester
A1 Kim, Hyun Je
A1 Kameyama, Naoya
A1 Estrada, Yeriel
A1 Der, Evan
A1 Krueger, James G
A1 Ruano, Juan
A1 Tuschl, Thomas
A1 Guttman-Yassky, Emma
K1 Atopic dermatitis
K1 T cells
K1 cytokines
K1 dendritic cells
K1 fibroblasts
K1 single-cell RNA sequencing
AB 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. 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. 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. 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. 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.
YR 2020
FD 2020-02-07
LK http://hdl.handle.net/10668/15077
UL http://hdl.handle.net/10668/15077
LA en
DS RISalud
RD Apr 17, 2025