Research press release



Immunology: How maternal inflammation contributes to behavioural abnormalities in mice



Jun Huh、Gloria Choiたちの研究グループは、仔マウスがMIA関連行動をとるようになる過程に母体の腸内細菌が寄与しているのかどうかを調べた。その結果、妊娠中のTh17細胞の産生を促進する腸内細菌が母体内に存在していると、その仔がMIA関連の行動異常を起こす確率が高くなることが判明した。特に、Th17細胞を誘導するマウスセグメント細菌やヒト共生細菌が定着したマウスが妊娠中に感染症にかかると、仔が神経発達症を発症するリスクが通常より高くなる可能性のあることが明らかになった。


上記2論文に記述された機構はヒトの自閉症とは関係ないが、「これらの論文は腸内細菌、免疫系、脳の発達の相互作用の複雑さを明らかにすることで貴重な手掛かりをもたらしていることに変わりはない」と同時掲載のCraig PowellのNews & Views論文に記されている。

Insights into how maternal inflammation can lead to the development of behavioural abnormalities in the offspring of mice are discussed in two papers published online in Nature this week.

Maternal immune activation (MIA) during pregnancy is known to contribute to behavioural abnormalities associated with neurodevelopmental disorders in both primate and rodent offspring. In humans, studies have suggested that the exposure of fetuses to maternal inflammation increases the likelihood of offspring developing autism spectrum disorder. Previous research in mice suggests that a molecule called interleukin-17a, produced by a group of T helper cells involved in multiple inflammatory conditions, called Th17 cells, could be involved. In pregnant mice, interleukin-17a induces behavioural as well as cortical abnormalities in the offspring if the mother undergoes immune system activation owing to infections or auto-inflammatory syndromes.

Jun Huh, Gloria Choi and colleagues investigated whether maternal gut bacteria contribute to the process that can lead to MIA-associated behaviours in the offspring of mice. The authors found that the presence of maternal intestinal bacteria that promote the production of Th17 cells during pregnancy meant that the offspring were more likely to have MIA-associated behavioural abnormalities. Specifically, they found that pregnant mice that had been colonized with the mouse segmented filamentous bacteria or human commensal bacteria, which induce intestinal Th17 cells, may increase the risk of neurodevelopmental disorders in the offspring, if the mother has an infection during pregnancy.

In the second study, Choi, Huh and co-authors identified the region of the mouse brain that mediates the behavioural abnormalities that were observed in offspring exposed to maternal inflammation. The authors localized the effects to a region encompassing the primary somatosensory cortex, which has been implicated in proprioceptive functions (relating to the awareness of the position of one’s body). They also found that reducing neural activity in the primary somatosensory cortex in offspring with MIA-associated neurodevelopmental disorders was sufficient to correct observed behavioural abnormalities.

Even if the mechanisms described are not involved in autism in humans, writes Craig Powell in an accompanying News & Views article, “these papers still provide valuable insights by revealing the complexity of the interactions between gut bacteria, the immune system and brain development.”

doi: 10.1038/nature23910 | 英語の原文

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