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. 2023 Aug;78(8):2215-2231.
doi: 10.1111/all.15781. Epub 2023 Jun 14.

Spatial transcriptomics combined with single-cell RNA-sequencing unravels the complex inflammatory cell network in atopic dermatitis

Yasutaka Mitamura  1 , Matthias Reiger  2   3   4 , Juno Kim  1 , Yi Xiao  1   5 , Damir Zhakparov  1   5 , Ge Tan  1 , Beate Rückert  1 , Arturo O Rinaldi  1 , Katja Baerenfaller  1   5 , Mübeccel Akdis  1 , Marie-Charlotte Brüggen  2   6   7 , Kari C Nadeau  8   9 , Patrick M Brunner  10 , Damian Roqueiro  5   11 , Claudia Traidl-Hoffmann  2   3   4   12 , Cezmi A Akdis  1   2
Affiliations

Spatial transcriptomics combined with single-cell RNA-sequencing unravels the complex inflammatory cell network in atopic dermatitis

Yasutaka Mitamura et al. Allergy. 2023 Aug.

Abstract

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with complex pathogenesis for which the cellular and molecular crosstalk in AD skin has not been fully understood.

Methods: Skin tissues examined for spatial gene expression were derived from the upper arm of 6 healthy control (HC) donors and 7 AD patients (lesion and nonlesion). We performed spatial transcriptomics sequencing to characterize the cellular infiltrate in lesional skin. For single-cell analysis, we analyzed the single-cell data from suction blister material from AD lesions and HC skin at the antecubital fossa skin (4 ADs and 5 HCs) and full-thickness skin biopsies (4 ADs and 2 HCs). The multiple proximity extension assays were performed in the serum samples from 36 AD patients and 28 HCs.

Results: The single-cell analysis identified unique clusters of fibroblasts, dendritic cells, and macrophages in the lesional AD skin. Spatial transcriptomics analysis showed the upregulation of COL6A5, COL4A1, TNC, and CCL19 in COL18A1-expressing fibroblasts in the leukocyte-infiltrated areas in AD skin. CCR7-expressing dendritic cells (DCs) showed a similar distribution in the lesions. Additionally, M2 macrophages expressed CCL13 and CCL18 in this area. Ligand-receptor interaction analysis of the spatial transcriptome identified neighboring infiltration and interaction between activated COL18A1-expressing fibroblasts, CCL13- and CCL18-expressing M2 macrophages, CCR7- and LAMP3-expressing DCs, and T cells. As observed in skin lesions, serum levels of TNC and CCL18 were significantly elevated in AD, and correlated with clinical disease severity.

Conclusion: In this study, we show the unknown cellular crosstalk in leukocyte-infiltrated area in lesional skin. Our findings provide a comprehensive in-depth knowledge of the nature of AD skin lesions to guide the development of better treatments.

Keywords: atopic dermatitis; single-cell transcriptomics; spatial transcriptomics; targeted proteomics.

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References

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