Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring.
Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring.
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DOI：
10.1038/nature23910
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发表时间：
2017-09-28
期刊：
影响因子：
64.8
通讯作者：
Huh JR
中科院分区：
文献类型：
--
作者：
Kim S;Kim H;Yim YS;Ha S;Atarashi K;Tan TG;Longman RS;Honda K;Littman DR;Choi GB;Huh JR
母体免疫激活（MIA）有助于灵长类动物和啮齿类动物后代与神经发育障碍相关的行为异常。在人类中，流行病学研究表明，胎儿暴露于母体炎症会增加患自闭症谱系障碍（ASD）的可能性。我们最近证明，由Th 17细胞产生的白细胞介素-17a（IL-17 a），参与多种炎症条件的CD 4 + T辅助效应细胞，在妊娠小鼠中诱导暴露于MIA的后代的行为以及皮质异常是必需的。然而，目前尚不清楚是否需要其他母体因素来促进MIA相关表型。此外，MIA导致母体循环中IL-17 α增加的T细胞活化的潜在机制尚未得到很好的理解。在这里，我们表明，MIA表型在后代需要母体肠道细菌，促进Th 17细胞分化。怀孕的小鼠，已与小鼠肠道分节丝状细菌（SFB）或人类肠道细菌，诱导肠道Th 17细胞的殖民地更有可能产生后代与MIA相关的异常。我们还表明，来自妊娠而非非妊娠女性的小肠树突状细胞（DC）在暴露于MIA后分泌IL-1β/IL-23/IL-6并刺激T细胞产生IL-17 α。总的来说，我们的数据表明，具有诱导Th 17细胞倾向的确定的肠道细菌可能会增加因感染或自身炎症综合征而经历免疫系统激活的孕妇后代神经发育障碍的风险。
Maternal immune activation (MIA) contributes to behavioral abnormalities associated with neurodevelopmental disorders in both primate and rodent offspring. In humans, epidemiological studies suggest that exposure of fetuses to maternal inflammation increases the likelihood of developing Autism Spectrum Disorder (ASD). We recently demonstrated that interleukin-17a (IL-17a) produced by Th17 cells, CD4+ T helper effector cells involved in multiple inflammatory conditions, is required in pregnant mice to induce behavioral as well as cortical abnormalities in the offspring exposed to MIA. However, it is unclear if other maternal factors are required to promote MIA-associated phenotypes. Moreover, underlying mechanisms by which MIA leads to T cell activation with increased IL-17a in the maternal circulation are not well understood. Here, we show that MIA phenotypes in offspring require maternal intestinal bacteria that promote Th17 cell differentiation. Pregnant mice that had been colonized with the mouse commensal segmented filamentous bacteria (SFB) or human commensal bacteria that induce intestinal Th17 cells were more likely to produce offspring with MIA-associated abnormalities. We also show that small intestine dendritic cells (DCs) from pregnant, but not from non-pregnant, females upon exposure to MIA secrete IL-1β/IL-23/IL-6 and stimulate T cells to produce IL-17a. Overall, our data suggest that defined gut commensal bacteria with a propensity to induce Th17 cells may increase the risk for neurodevelopmental disorders in offspring of pregnant mothers undergoing immune system activation due to infections or autoinflammatory syndromes.
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DOI：
10.1056/nejmoa1307491
发表时间：
2014-03-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
Stoner R;Chow ML;Boyle MP;Sunkin SM;Mouton PR;Roy S;Wynshaw-Boris A;Colamarino SA;Lein ES;Courchesne E
通讯作者：
Courchesne E
影响因子：
15.1
作者：
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通讯作者：
Patterson, Paul H.
DOI：
10.1126/science.aac4255
发表时间：
2015-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Sivan A;Corrales L;Hubert N;Williams JB;Aquino-Michaels K;Earley ZM;Benyamin FW;Lei YM;Jabri B;Alegre ML;Chang EB;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
64.8
作者：
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通讯作者：
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影响因子：
10.6
作者：
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通讯作者：
Bauman MD