High Glucose Intake Exacerbates Autoimmunity through Reactive-Oxygen-Species-Mediated TGF-β Cytokine Activation.
High Glucose Intake Exacerbates Autoimmunity through Reactive-Oxygen-Species-Mediated TGF-β Cytokine Activation.
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DOI：
10.1016/j.immuni.2019.08.001
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发表时间：
2019-10-15
期刊：
影响因子：
32.4
通讯作者：
Chen, WanJun
中科院分区：
文献类型：
--
作者：
Zhang, Dunfang;Jin, Wenwen;Wu, Ruiqing;Li, Jia;Park, Sang-A;Tu, Eric;Zanyit, Peter;Xu, Junji;Liu, Ousheng;Cain, Alexander;Chen, WanJun
饮食被认为是自身免疫性疾病发病率增加的一个潜在环境风险因素，但其潜在机制仍然难以捉摸。在这里，我们表明，高葡萄糖摄入加剧了结肠炎和实验性自身免疫性脑脊髓炎（EAE）小鼠模型的自身免疫。我们阐明了大量的葡萄糖通过上调T细胞中的活性氧（ROS）从其潜伏形式激活转化生长因子-β（TGF-β）而特异性地促进T辅助性-17（Th 17）细胞分化。我们进一步确定线粒体ROS（mtROS）是高糖诱导的TGF-β活化和Th 17细胞生成的关键。因此，我们揭示了一个以前未被认识到的机制，高葡萄糖摄入的不良影响，在自身免疫和炎症的发病机制。高葡萄糖摄入会增加许多疾病的风险，但对自身免疫的影响仍然难以捉摸。Zhang等人表明，高葡萄糖摄入通过诱导Th 17细胞而加剧自身免疫。高糖通过ROS依赖性TGF-β激活诱导Th 17细胞，揭示了自身免疫中高糖摄入的未识别机制。
Diet has been suggested to be a potential environmental risk factor for the increasing incidence of autoimmune diseases, yet the underlying mechanisms remain elusive. Here we show that high glucose intake exacerbated autoimmunity in mouse models of colitis and experimental autoimmune encephalomyelitis (EAE). We elucidated that high amounts of glucose specifically promoted T helper-17 (Th17) cell differentiation by activating transforming growth factor-β (TGF-β) from its latent form through upregulation of reactive oxygen species (ROS) in T cells. We further determined that mitochondrial ROS (mtROS) are key for high glucose induced TGF-β activation and Th17 cell generation. We have thus revealed a previously unrecognized mechanism underlying the adverse effects of high glucose intake in the pathogenesis of autoimmunity and inflammation. High glucose intake increases the risk of many diseases, yet the effects to autoimmunity remain elusive. Zhang et al. show that high glucose intake exacerbates autoimmunity by inducing Th17 cells. High glucose induces Th17 cells through ROS-dependent TGF-β activation, revealing unrecognized mechanisms for high glucose intake in autoimmunity.
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影响因子：
17.1
作者：
Kasagi, Shimpei;Zhang, Pin;Chen, WanJun
通讯作者：
Chen, WanJun
DOI：
10.1038/nri3423
发表时间：
2013-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
30.5
作者：
Manel, Nicolas;Unutmaz, Derya;Littman, Dan R.
通讯作者：
Littman, Dan R.