关键词: 皮炎, 特应性, 树突细胞, 上皮细胞, 转录组, 炎症性树突状表皮细胞, 单细胞转录组测序, 免疫代谢

Abstract: 【Abstract】 Objective To compare single-cell transcriptome sequencing data from skin samples of patients with atopic dermatitis（AD） and those from skin samples of healthy controls, and to investigate immunometabolic characteristics of inflammatory dendritic epidermal cells （IDECs） in skin lesions of patients with AD. Methods An in-depth analysis was carried out on previously published single-cell sequencing data from 8 AD patients and 7 healthy controls in the Gene Expression Omnibus database （GSE 153760）. Marker genes were used to screen out IDECs, and differentially expressed genes in IDECs between the two groups were obtained. Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed on these differentially expressed genes, the“AddModuleScore”function in the Seurat package was used to evaluate the IDEC-involving inflammatory and metabolic pathways in the two groups, and Mann-Whitney rank sum test was used for statistical analysis; correlations between the IDEC-involved metabolic and inflammatory pathways were evaluated using the above scores and the "cor" and "cor.test" functions in R packages. Results A large number of IDECs infiltrating the skin lesions of AD patients highly expressed Th2 chemokines （CCL17）, antigen presentation-related genes （CD1B）, endothelial growth-related genes （TYMP, AREG）, inflammation-related genes （S100A8, S100A10, LGALS1）, stromal fibrosis-related genes （MMP12, ADAM19）, metabolism-related genes （LDHA, LIPA, GLUL）, and danger signaling-related genes （HSPA1B, HSP90AA1, HSPB1, HSPH1）. The activities of glucose energy metabolism, glycolytic metabolism, nucleotide metabolism, glutamate and glutamine metabolism, and amino acid metabolism were significantly upregulated in IDECs in AD patients, and was positively correlated with Th2 inflammation levels; the activities of oxidative phosphorylation and lipid metabolism was significantly downregulated in IDECs in AD patients, and the lipid metabolism level was negatively correlated with Th2 inflammation levels. Glutamine metabolism and glucose energy metabolism were positively correlated with Th22 inflammation levels; Th1 inflammation and Th17 inflammation were negatively correlated with pentose phosphate metabolism, nucleotide metabolism, glycolytic metabolism, and amino acid metabolism pathways. Conclusion The inflammation- and metabolism-related genes were abnormally expressed in IDECs in skin lesions of AD patients, and activities of multiple metabolic pathways were markedly upregulated in IDECs, among which glycolysis metabolism activity was mostly correlated with Th2 inflammation levels.

Key words: Dermatitis, atopic, Dendritic cells, Epithelial cells, Transcriptome, Inflammatory dendritic epidermal cells, Single-cell transcriptome sequencing, Immunometabolism