Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt
Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt
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DOI：
10.1126/sciadv.abe4827
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发表时间：
2021-01-01
期刊：
影响因子：
13.6
通讯作者：
Lu, Zhengqi
中科院分区：
文献类型：
--
作者：
Cai, Wei;Chen, Xiaodong;Lu, Zhengqi
肠道微生物群塑造宿主免疫系统并影响各种神经系统疾病的结果。动脉硬化性脑血管病（aCSVD）在老年人中高发，其病理机制尚不完全清楚。目前的研究调查了aCSVD患者肠道微生物群的生态学，特别是其对宿主免疫系统的影响。我们报道了肠道微生物群组成的改变与不良疾病结局和炎症状态加剧有关。当暴露于aCSVD患者的粪便细菌提取物时，人和小鼠的中性粒细胞被激活，白细胞介素- 17a （IL-17A）的产生能力增加。机制上，中性粒细胞中的ROR γ t信号被acsvd相关肠道细菌提取物激活，从而上调IL-17A的产生。我们的研究结果揭示了以前未被认识到的肠-免疫-脑轴在aCSVD病理生理中的意义，具有治疗意义。
The intestinal microbiota shape the host immune system and influence the outcomes of various neurological disorders. Arteriosclerotic cerebral small vessel disease (aCSVD) is highly prevalent among the elderly with its pathological mechanisms yet is incompletely understood. The current study investigated the ecology of gut microbiota in patients with aCSVD, particularly its impact on the host immune system. We reported that the altered composition of gut microbiota was associated with undesirable disease outcomes and exacerbated inflammaging status. When exposed to the fecal bacterial extracts from a patient with aCSVD, human and mouse neutrophils were activated, and capacity of interleukin-17A (IL-17A) production was increased. Mechanistically, ROR gamma t signaling in neutrophils was activated by aCSVD-associated gut bacterial extracts to up-regulate IL-17A production. Our findings revealed a previously unrecognized implication of the gut-immune-brain axis in aCSVD pathophysiology, with therapeutic implications.