Bacterial-induced maternal interleukin 17A pathway promotes autistic-like behaviors in mouse offspring

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19657
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: Fukuoka Dental College
• Principal Investigator: Tanaka Yoshihiko 福岡歯科大学, 口腔歯学部, 教授 (00398083)
• Co-Investigator(Kenkyū-buntansha): 永尾 潤一 福岡歯科大学, 口腔歯学部, 講師 (30509047) ; 成田 由香 福岡歯科大学, 口腔歯学部, 助教 (50758050) ; 長 環 福岡歯科大学, 口腔歯学部, 客員教授 (90131870) ; 有田 健一 福岡歯科大学, 口腔歯学部, 助教 (90780205)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 自閉スペクトラム症 / 脳神経系 / 免疫系 / 細菌感染

Outline of Final Research Achievements

Maternal immune activation (MIA) by an infection is considered to be an important environmental factor of fetal brain development. Recent animal model on MIA induced by a mimic of viral infection, demonstrates that maternal interleukin-17A (IL-17A) signaling is required for the development of autism spectrum disorder (ASD)-like behaviors of offspring. However, there is little information on bacterial infection. In this study, we demonstrated that lipopolysaccharide (LPS)-induced MIA promoted ASD-like behaviors in mouse offspring. We further found that LPS exposure induced acute phase immune response: elevation of serum IL-17A levels in MIA mothers and upregulation of IL-17R mRNA expression in the fetal brain. Blocking of IL-17A in LPS-induced MIA ameliorated ASD-like behaviors in offspring. Our data suggest that bacterial-induced maternal IL-17A pathway promotes ASD-like behaviors in offspring.

Free Research Field

病態系口腔科学

Academic Significance and Societal Importance of the Research Achievements

母体マウスに細菌抽出物で擬似感染させたところ、仔マウスが自閉症様行動を示すようになりました。母体ではインターロイキン-17Aが上昇しており、中和抗体で除去すると健常な仔マウスが誕生することが分かりました。母体の細菌感染による免疫応答が胎児の脳神経発達に関連することを意味します。本研究によって、自閉症の原因の一つが妊娠中の細菌感染であることが動物実験で明らかになりました。