Zhao Jing, Liu Jing, Denney James, Li Chen, Li Fang, Chang Fen, Chen Mingyou, Yin Deling
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, China.
Neuroimmunomodulation. 2015;22(5):328-36. doi: 10.1159/000371468. Epub 2015 Feb 25.
Stress, either physical or psychological, can have a dramatic impact on our immune system. There has been little progress, however, in understanding chronic stress-induced immunosuppression. Naive CD4+ T cells could modulate immune responses via differentiation to T helper (Th) cells. In this study, we showed that stress promotes the release of the Th1 cytokines interferon (IFN)-γ and tumor necrosis factor (TNF)-α, the Th2 cytokines interleukin (IL)-4 and IL-10 and the Th17 cytokine IL-17 of splenic naive CD4+ T cells. This suggests that stress promotes the differentiation of naive CD4+ T cells to Th1, Th2 and Th17 cells. Knockout strategies verified that TLR2 might modulate the differentiation of Th1/Th2 cells by inhibiting p38 mitogen-activated protein kinase (MAPK). Taken together, our data suggest that chronic stress induces immune suppression by targeting TLR2 and p38 MAPK in naive CD4+ T cells.
身体或心理上的压力都会对我们的免疫系统产生巨大影响。然而,在理解慢性应激诱导的免疫抑制方面进展甚微。初始CD4+ T细胞可通过分化为辅助性T(Th)细胞来调节免疫反应。在本研究中,我们发现应激促进脾脏初始CD4+ T细胞释放Th1细胞因子干扰素(IFN)-γ和肿瘤坏死因子(TNF)-α、Th2细胞因子白细胞介素(IL)-4和IL-10以及Th17细胞因子IL-17。这表明应激促进初始CD4+ T细胞向Th1、Th2和Th17细胞分化。基因敲除策略证实,Toll样受体2(TLR2)可能通过抑制p38丝裂原活化蛋白激酶(MAPK)来调节Th1/Th2细胞的分化。综上所述,我们的数据表明,慢性应激通过靶向初始CD4+ T细胞中的TLR2和p38 MAPK诱导免疫抑制。