Cai Zhitao, Liu Hong, Wu Xiongfei
Department of Nephrology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China.
BMC Immunol. 2017 Mar 10;18(1):16. doi: 10.1186/s12865-017-0198-8.
Regulatory T (Treg) cells play important roles in autoimmune diseases, cancer, and organ transplantation. Forkhead box protein o1 (Foxo1) and IL-7Rα(CD127) are closely related to the homeostasis of Treg cells. However, the mechanism underlying Treg proliferation and activation remains unclear. Here, we evaluated how the over-expression of Foxo1 affects Treg cell proliferation via intracellular signaling. nTreg cells were transfected separately with Foxo1 and Aven small-interfering RNA (siRNA) or over-expression plasmid. The expression of signaling pathway genes and CD127 was confirmed using RT-qPCR and western blot analysis. The expression of cell surface molecules and apoptosis was confirmed by Flow Cytometry 3-(4, 5-Dimethylthiazol-2-yl) 2,5- diphenyltetrazolium bromide for cell proliferation assays.
Foxo1 strengthened the proliferative ability of Treg cells by activating IL-7/CD127 signaling. In addition, Foxo1 suppressed Treg cell apoptosis by regulating Aven expression.
The results in this study indicated that Foxo1 is a positive regulatory factor for the proliferation and activity of Treg cells. Foxo1 might be a potential target for the activation of nTreg cells in vivo and in vitro.
调节性T(Treg)细胞在自身免疫性疾病、癌症和器官移植中发挥着重要作用。叉头框蛋白o1(Foxo1)和IL-7Rα(CD127)与Treg细胞的稳态密切相关。然而,Treg细胞增殖和激活的潜在机制仍不清楚。在此,我们评估了Foxo1的过表达如何通过细胞内信号传导影响Treg细胞增殖。将天然Treg(nTreg)细胞分别用Foxo1和Aven小干扰RNA(siRNA)或过表达质粒转染。使用逆转录定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹分析来确认信号通路基因和CD127的表达。通过流式细胞术、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法检测细胞表面分子表达和细胞凋亡情况,以进行细胞增殖测定。
Foxo1通过激活IL-7/CD127信号增强Treg细胞的增殖能力。此外,Foxo1通过调节Aven表达抑制Treg细胞凋亡。
本研究结果表明,Foxo1是Treg细胞增殖和活性的正调控因子。Foxo1可能是体内外激活天然Treg细胞的潜在靶点。