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叉头框转录因子1通过控制Aven的表达来影响自然调节性T细胞的凋亡。

Forkhead-box transcription factor 1 affects the apoptosis of natural regulatory T cells by controlling Aven expression.

作者信息

Cai Zhitao, Liu Hong, Wu Xiongfei

机构信息

Department of Nephrology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China.

出版信息

BMC Immunol. 2017 Mar 10;18(1):16. doi: 10.1186/s12865-017-0198-8.

Abstract

BACKGROUND

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

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。

结果

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。

结论

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。

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