Chronic stress promotes lymphocyte reduction through TLR2 mediated PI3K signaling in a β-arrestin 2 dependent manner.
Chronic stress promotes lymphocyte reduction through TLR2 mediated PI3K signaling in a β-arrestin 2 dependent manner.
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慢性应激通过TLR2介导的PI3K信号传导促进淋巴细胞的减少。
DOI：
10.1016/j.jneuroim.2010.11.015
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发表时间：
2011-04
影响因子：
3.3
通讯作者：
Yin, Deling
中科院分区：
文献类型：
--
作者：
Li, Hui;Chen, Lin;Zhang, Ying;LeSage, Gene;Zhang, Yi;Wu, Yan;Hanley, Gregory;Sun, Shenggang;Yin, Deling
生理和心理压力可以改变人类和动物的免疫系统。众所周知，压力是许多人类疾病的风险因素，如感染性疾病、自身免疫性疾病和癌症。toll样受体（TLRs）在诱导先天和适应性免疫反应中起着关键作用。我们之前的研究表明，TLR4缺乏可防止应激诱导的脾细胞减少。然而，TLR2在应激介导的淋巴细胞减少中的作用尚不清楚。在这项研究中，我们研究了TLR2配体对应激诱导的淋巴细胞减少的影响。我们还确定了磷酸肌苷3激酶(pi3k)/Akt通路是否参与tlr2介导的淋巴细胞数量在应激下的改变。我们的数据表明，TLR2配体肽聚糖（PGN）或Pam3Csk4 （Pam3）刺激TLR2可减弱应激诱导的淋巴细胞数量减少。然而，TLR2配体对应激性淋巴细胞减少的保护作用在TLR2缺乏症小鼠中丧失。此外，PGN对TLR2的刺激可通过PI3K诱导应激诱导的脾细胞数量减少。此外，PGN通过pi3k依赖的方式显著提高Akt的磷酸化水平。此外，我们发现PGN刺激TLR2诱导应激诱导的脾细胞数量减少在β-抑制蛋白2缺陷小鼠中被消除。此外，在应激诱导的细胞因子水平变化中，pgnn诱导的免疫保护似乎需要β-阻滞蛋白2，一种多功能适配器和信号传感器。综上所述，我们的研究表明，刺激tlr2介导的PI3K信号可以减轻应激引起的脾细胞减少，而β-阻滞蛋白2可以调节应激后tlr2介导的免疫反应。
Physical and psychological stress can alter the immune system in both humans and animals. Stress is a known risk factor for numerous human diseases, such as infectious and autoimmune diseases, and cancer. Toll-like receptors (TLRs) play a pivotal role in the induction of innate and adaptive immune response. Our previous studies have shown that TLR4 deficiency prevents stress-induced splenocyte reduction. However, the role of TLR2 in stress-mediated lymphocyte reduction is unknown. In this study, we investigated the effects of TLR2 ligands on stress-induced lymphocyte reduction. We also defined whether the phosphoinositide 3-kinases (PI3Ks)/Akt pathway contributes to TLR2-mediated lymphocyte numbers altered by stress. Our data have shown that stimulation of TLR2 by TLR2 ligands peptidoglycan (PGN) or Pam3Csk4 (Pam3) attenuates stress-induced reduction in lymphocyte numbers. However, TLR2 ligand-induced protection from stress-induced lymphocyte reduction is lost in TLR2 deficiency in mice. Furthermore, stimulation of TLR2 by PGN induces protection from stress-induced reduction in the number of splenocytes through PI3K. Moreover, PGN dramatically increases the level of phosphorylation of Akt through a PI3K-dependent manner. Moreover, we found that stimulation of TLR2 by PGN induced protection from stress-induced reduction in splenocyte numbers is abolished in β-arrestin 2 deficient mice. In addition, PGN-induced immune protection in stress-induced changes of cytokine levels appears to require β-arrestin 2, a multifunctional adaptor and signal transducer. Collectively, our study thus demonstrates that stimulation of TLR2-mediated PI3K signaling attenuates splenocyte reduction induced by stress, and that β-arrestin 2 modulates TLR2-mediated immune response following stress.
影响因子：
8.6
作者：
Wang, Xinran;Ouyang, Yijian;Dai, Hongjie
通讯作者：
Dai, Hongjie