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

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

doi:10.1016/j.isci.2023.106729

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

iScience. 2023 Apr 23;26(5):106729. doi: 10.1016/j.isci.2023.106729. eCollection 2023 May 19.

Authors

Yuehan Gao¹, Runping Duan¹, He Li¹, Loujing Jiang¹, Tianyu Tao¹, Xiuxing Liu¹, Lei Zhu¹, Zhaohuai Li¹, Binyao Chen¹, Songguo Zheng², Xianchai Lin¹, Wenru Su¹

Affiliations

¹ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 51000, China.
² The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 51000, China.

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.

Keywords: Immunology; Stem cells research; Transcriptomics.