在自身免疫中,从 Foxp3 前体细胞产生 RORγt 抗原特异性 T 调节 17 细胞。
Generation of RORγt Antigen-Specific T Regulatory 17 Cells from Foxp3 Precursors in Autoimmunity.
机构信息
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USA; Laboratory of Immune Regulation, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
出版信息
Cell Rep. 2017 Oct 3;21(1):195-207. doi: 10.1016/j.celrep.2017.09.021.
Th17 cells are potent mediators in autoimmune diseases, and RORγt is required for their development. Recent studies have shown that RORγt Treg cells in the gut regulate intestinal inflammation by inhibiting effector T cell function. In the current study, we report that RORγt Treg cells were also found in lymph nodes following immunization. Not only distinct from intestinal RORγt Treg cells in their transcriptomes, peripheral RORγt Treg cells were derived from Foxp3 thymic Treg cells in an antigen-specific manner. Development of these RORγt Treg cells, coined T regulatory 17 (Tr17) cells, depended on IL-6/Stat3 signaling. Tr17 cells showed suppressive activity against antigen-specific effector T cells in vitro. In addition, Tr17 cells efficiently inhibited myelin-specific Th17-cell-mediated CNS auto-inflammation in a passive EAE model. Collectively, our study demonstrates that Tr17 cells are effector Treg cells that potentially restrict autoimmunity.
Th17 细胞是自身免疫性疾病的有力介质,而 RORγt 是其发展所必需的。最近的研究表明,肠道中的 RORγt Treg 细胞通过抑制效应 T 细胞的功能来调节肠道炎症。在本研究中,我们报告称,在免疫接种后也可以在淋巴结中发现 RORγt Treg 细胞。外周 RORγt Treg 细胞不仅在转录组上与肠道 RORγt Treg 细胞明显不同,而且还以抗原特异性的方式来自 Foxp3 胸腺 Treg 细胞。这些 RORγt Treg 细胞的发育,被称为 T 调节性 17(Tr17)细胞,依赖于 IL-6/Stat3 信号通路。Tr17 细胞在体外对抗原特异性效应 T 细胞具有抑制活性。此外,Tr17 细胞在被动 EAE 模型中有效抑制了髓鞘特异性 Th17 细胞介导的中枢神经系统自身炎症。总之,我们的研究表明,Tr17 细胞是效应性 Treg 细胞,可能限制自身免疫。