TGF-β1/Smad2/3/Foxp3 signaling is required for chronic stress-induced immune suppression.
TGF-β1/Smad2/3/Foxp3 signaling is required for chronic stress-induced immune suppression.
复制标题
DOI：
10.1016/j.jneuroim.2017.11.005
复制
发表时间：
2018-01-15
影响因子：
3.3
通讯作者：
Yin D
中科院分区：
文献类型：
--
作者：
Zhang H;Caudle Y;Wheeler C;Zhou Y;Stuart C;Yao B;Yin D
根据持续时间和严重程度，心理紧张和身体压力可以增强或抑制人类和动物的免疫系统。虽然已经确定慢性应激对免疫功能有显著的抑制作用，但其影响免疫反应的机制尚不清楚。通过小鼠体内系统，我们发现TGF-β1/Smad2/3/Foxp3轴在慢性应激后被显著激活。此外，TLR9和p38 MAPK在TGF-β1/Smad2/3/Foxp3信号级联的激活中发挥了关键作用。此外，抑制TGF-β1/Smad2/3/Foxp3或p38可显著减弱慢性应激诱导的淋巴细胞凋亡和凋亡相关蛋白，以及脾脏T调节细胞的分化。有趣的是，慢性应激引起的促炎和抗炎细胞因子平衡失衡也可以通过阻断TGF-β1/Smad2/3/Foxp3轴来恢复。这些发现揭示了慢性应激调节免疫功能的新机制，并为开发新型抗免疫抑制药物确定了新的靶点。
Depending on the duration and severity, psychological tension and physical stress can enhance or suppress the immune system in both humans and animals. Although it has been established that chronic stress exerts a significant suppressive effect on immune function, the mechanisms by which affects immune responses remain elusive. By employing an in vivo murine system, we revealed that TGF-β1/Smad2/3/Foxp3 axis was remarkably activated following chronic stress. Furthermore, TLR9 and p38 MAPK played a critical role in the activation of TGF-β1/Smad2/3/Foxp3 signaling cascade. Moreover, inhibition of TGF-β1/Smad2/3/Foxp3 or p38 significantly attenuated chronic stress-induced lymphocyte apoptosis and apoptosis-related proteins, as well as the differentiation of T regulatory cells in spleen. Interestingly, disequilibrium of pro-inflammatory and anti-inflammatory cytokines balance caused by chronic stress was also rescued by blocking TGF-β1/Smad2/3/Foxp3 axis. These findings yield insight into a novel mechanism by which chronic stress modulates immune functions and identifies new targets for the development of novel anti-immune suppressant medications.
登录
查看更多内容
影响因子：
4.6
作者：
Caraci F;Gulisano W;Guida CA;Impellizzeri AA;Drago F;Puzzo D;Palmeri A
通讯作者：
Palmeri A
影响因子：
1
作者：
Li, Chun;Li, Haixia;Gai, Xiaodong
通讯作者：
Gai, Xiaodong
影响因子：
4.8
作者：
Hayashida, T;deCaestecker, M;Schnaper, HW
通讯作者：
Schnaper, HW
影响因子：
4.8
作者：
Li, Hui;Hu, Dan;Yin, Deling
通讯作者：
Yin, Deling
影响因子：
4.4
作者：
Dhabhar, Firdaus S.
通讯作者：
Dhabhar, Firdaus S.