Single-cell analysis of immune cells on gingiva-derived mesenchymal stem cells in experimental autoimmune uveitis

实验性自身免疫性葡萄膜炎中牙龈间充质干细胞上免疫细胞的单细胞分析

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作者:Yuehan Gao ,Runping Duan ,He Li ,Loujing Jiang ,Tianyu Tao ,Xiuxing Liu ,Lei Zhu ,Zhaohuai Li ,Binyao Chen ,Songguo Zheng ,Xianchai Lin ,Wenru Su

Abstract

Gingiva-derived mesenchymal stem cells (GMSCs) have shown astonishing efficacy in the treatment of various autoimmune diseases. However, the mechanisms underlying these immunosuppressive properties remain poorly understood. Here, we generated a lymph node single-cell transcriptomic atlas of GMSC-treated experimental autoimmune uveitis mice. GMSC exerted profound rescue effects on T cells, B cells, dendritic cells, and monocytes. GMSCs rescued the proportion of T helper 17 (Th17) cells and increased the proportion of regulatory T cells. In addition to globally altered transcriptional factors (Fosb and Jund), we observed cell type-dependent gene regulation (e.g., Il17a and Rac1 in Th17 cells), highlighting the GMSCs' cell type-dependent immunomodulatory capacity. GMSCs strongly influenced the phenotypes of Th17 cells, suppressing the formation of the highly inflammatory CCR6-CCR2+ phenotype and enhancing the production of interleukin (IL) -10 in the CCR6+CCR2+ phenotype. Integration of the glucocorticoid-treated transcriptome suggests a more specific immunosuppressive effect of GMSCs on lymphocytes.

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