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

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 10× 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 (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.

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.