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

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

Publication date: Available online 7 February 2020

Source: Journal of Allergy and Clinical Immunology

Author(s): Helen He, Hemant Suryawanshi, Pavel Morozov, Jesús Gay-Mimbrera, Ester Del Duca, Hyun Je Kim, Naoya Kameyama, Yeriel Estrada, Evan Der, James G. Krueger, Juan Ruano, Thomas Tuschl, Emma Guttman-Yassky

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.

Graphical abstract