Epithelial Barrier Theory

Original articles

Spatial and single-cell RNA-sequencing, the cutting-edge technologies for the investigation of the disease pathogenesis

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

Mitamura Y, Reiger M, Kim J, Xiao Y, Zhakparov D, Tan G, Rückert B, Rinaldi AO, Baerenfaller K, Akdis M, Brüggen MC, Nadeau KC, Brunner PM, Roqueiro D, Traidl-Hoffmann C, Akdis CA. Allergy. 2023 Aug;78(8):2215-2231. doi: 10.1111/all.15781.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases affecting the lives of more than 500 million people worldwide. Representative symptoms are dry, itchy, sensitive skin with redness with the skin barrier dysfunction. Recent advances, including single-cell RNA-sequencing analyses, showed the details of AD’s molecular and immunological characterization. However, even within the realm of single-cell studies, the dimensions of spatial arrangement were unclear.

The human body has approximately 200 different cell types. Spatial transcriptomics is a novel technology that integrates whole transcriptomics data and information on the localization of the cells. To investigate how do these cells converse and collaborate within the skin’s intricate landscape, Mitamura et al. collected gene expression information from more than 16,000 spots in tissue from AD patients and healthy controls. This study identified the detailed cell-cell crosstalk in the AD skin. Besides, the combination of the result of cutting-edge technologies (Spatial transcriptomics, single-cell transcriptomics, targeted multiple proteomics) demonstrated AD specific CCL13+, CCL18+, M2 macrophages, activated dendritic cells (CCR7+, CCL17,  LAMP3+), and activated fibroblast (CCL19+, TNC+, COL6A5+). The spatial transcriptome identified the interaction between these M2 macrophages, dendritic cells, fibroblasts, and T cells. Moreover, serum levels of TNC and CCL18 showed positive correlation with AD severity, suggesting that they are possible candidate biomarkers for AD.

Identifying the AD-specific activated cells and demonstrating their cellular interactions may lead to unknown pathogenesis of AD and novel treatment for AD. Implementing the findings in other areas, especially the epithelial layer, is a promising approach for investigating the mechanism of epithelial barrier dysfunction. Read more.