Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells.
Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells.
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DOI：
10.1038/nm.4068
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发表时间：
2016-05
期刊：
影响因子：
82.9
通讯作者：
Anrather J
中科院分区：
文献类型：
--
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
共生肠道细菌会影响宿主的免疫系统，并可能影响包括大脑在内的几个器官的疾病进程。然而，目前尚不清楚微生物群是否对急性脑损伤的结果产生影响。在这里，我们表明，粪便诱导的肠道植物群的改变减少了小鼠的缺血性脑损伤，这是一种可通过粪便移植传播的效应。肠道生态失调通过改变树突状细胞活性改变小肠中的免疫稳态，导致调节性T细胞增加和IL-17+ γδ T细胞减少。失调抑制中风后效应T细胞从肠道到软脑膜的运输。白细胞介素-10（IL-10）和IL-17是肠生态失调所提供的神经保护所必需的。这些发现揭示了以前未被认识到的肠-脑轴以及肠植物群和脑膜IL-17+ γδ T细胞对缺血性损伤的影响。
Commensal gut bacteria impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the microbiota has an impact on the outcome of acute brain injury. Here we show that antibiotic-induced alterations in the intestinal flora reduces ischemic brain injury in mice, an effect transmissible by fecal transplants. Intestinal dysbiosis alters immune homeostasis in the small intestine leading to an increase in regulatory T cells and a reduction in IL-17+ γδ T cells, through altered dendritic cell activity. Dysbiosis suppresses trafficking of effector T cells from the gut to the leptomeninges after stroke. Interleukin-10 (IL-10) and IL-17 are required for the neuroprotection afforded by intestinal dysbiosis. The findings reveal a previously unrecognized gut-brain axis and the impact of the intestinal flora and meningeal IL-17+ γδ T cells on ischemic injury.