The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring.
The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring.
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DOI：
10.1126/science.aad0314
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发表时间：
2016-02-26
期刊：
影响因子：
--
通讯作者：
Huh JR
中科院分区：
文献类型：
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作者：
Choi GB;Yim YS;Wong H;Kim S;Kim H;Kim SV;Hoeffer CA;Littman DR;Huh JR
怀孕期间的病毒感染与后代自闭症谱系障碍（ASD）的频率增加有关。这一观察结果已在经历母体免疫激活（MIA）的啮齿动物中建模。MIA模型中关键的免疫细胞群尚未确定。在小鼠中使用遗传突变体和阻断抗体，我们表明视黄酸受体相关孤儿核受体γt（RORγt）依赖性效应T淋巴细胞[例如，辅助性T细胞17（TH 17）和效应细胞因子白细胞介素-17 α（IL-17 α）是MIA诱导的后代行为异常所必需的。我们发现，MIA诱导异常的皮质表型，这也是依赖于母亲的IL-17 a，在胎儿的大脑。我们的数据表明，在易感孕妇中靶向治疗TH 17细胞可能会降低生育炎症诱导的ASD样表型儿童的可能性
Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor–related orphan nuclear receptor γt (RORγt)–dependent effector T lymphocytes [e.g., T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes