Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Immunol Lett. 2020 Sep;225:16-22. doi: 10.1016/j.imlet.2020.06.006. Epub 2020 Jun 15.
Mouse mesenchymal stem cells (MSCs) have been shown to suppress T cells. Especially, MSC-cultured media have shown suppressive functions against various immune cells including the T cells. However, the underlying immunosuppressive mechanisms of the MSC-cultured medium are not yet fully understood. In this study, we confirmed the T cell-suppression capacity of MSC culture supernatant (MSC-CS) through both apoptosis and cell cycle arrest, and hypothesized that the exosomes were the major immunosuppressive agents in the MSC-CS. MSC-derived exosomes (MSC-exo) exhibited potent suppressive effects on T cell proliferation while the rest of the supernatant fraction did not. Interestingly, the exosomes derived from MSC only induced the cell cycle arrest, and it was through the upregulation of p27kip1 protein and downregulation of Cdk2 protein. In conclusion, the exosomes secreted from MSCs could suppress the activated T cell proliferation through the induction of cell cycle arrest.
鼠间充质干细胞（MSCs）已被证明具有抑制 T 细胞的作用。特别是，MSC 培养的培养基已显示出对包括 T 细胞在内的各种免疫细胞的抑制功能。然而，MSC 培养物培养基的潜在免疫抑制机制尚不完全清楚。在这项研究中，我们通过细胞凋亡和细胞周期阻滞证实了 MSC 培养上清（MSC-CS）的 T 细胞抑制能力，并假设外泌体是 MSC-CS 中的主要免疫抑制因子。MSC 来源的外泌体（MSC-exo）对 T 细胞增殖具有强烈的抑制作用，而其余上清部分则没有。有趣的是，仅 MSC 来源的外泌体诱导细胞周期阻滞，这是通过上调 p27kip1 蛋白和下调 Cdk2 蛋白实现的。总之，MSC 分泌的外泌体可以通过诱导细胞周期阻滞来抑制激活的 T 细胞增殖。
