Regulation of retrotransposable elements in the mammalian neuron by Interleukin family members

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22368
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 42:Veterinary medical science, animal science, and related fields
• Research Institution: Hiroshima University (2020); Kyushu University (2019)
• Principal Investigator: Imamura Takuya 広島大学, 統合生命科学研究科(理), 教授 (90390682)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: レトロトランスポゾン / インターロイキン / IL17D

Outline of Final Research Achievements

Maternal immune activation (MIA) promotes the abnormal cortical formation that causes the incidence of autism spectrum disorder in offspring. IL-17 cytokine family members, especially Interleukin-17A (IL-17A) produced by Th17 cells, have been believed to mediate this phenomenon through NF-kB pathway. We find unexpected pattern of interleukin-17D (IL-17D) expression in neural stem/precursor cells. It increases during mouse brain development, raising the possibility that IL-17D has a supportive function differently from IL-17A. Functional studies indicated that apoptotic cells increased after Il17d knockdown and exogenous IL-17D can protect from MIA-induced abnormal cortical formation in the fetal brain through MEK pathway. Our data suggest that neural IL-17D supports normal brain development in offspring to resist against maternally derived inflammatory IL-17A signals.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

今回、マウスを活用した研究により、医療や動物生産に向けたインターロイキン類の新しい利用法が提案できた。妊娠時の胎児の健康管理は緊喫の課題であり、全ての脳細胞の根幹をなすゲノムについて、その崩壊を末梢投与により簡便に食い止めることができる可能性が出てきたことにより、今後は、IL17Dを含むインターロイキン類の制御により母体の免疫を管理することで、出生児の統合失調症発症リスクを根本から抑える方法論の開発が期待できる。