Clarification of central nervous system disorders caused by specific T cell subsets

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K06918
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: University of Tsukuba
• Principal Investigator: Takei Yosuke 筑波大学, 医学医療系, 教授 (20272487)
• Co-Investigator(Kenkyū-buntansha): 佐々木 哲也 筑波大学, 医学医療系, 准教授 (10634066) ; 岩田 卓 筑波大学, 医学医療系, 助教 (80855883)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: Th17細胞 / 母体免疫活性化 / IL-17A / 自閉スペクトラム症 / ミクログリア

Outline of Final Research Achievements

The elevation of maternal retinoic acid-related orphan receptor γt leads to excessive activation of Th17 cells, altering immune responsiveness and increasing the rate of miscarriage during pregnancy. When IL-17A produced by Th17 cells is directly administered into the cerebral ventricles of mice, glial cells exhibit abnormal properties, revealing a part of the mechanism that causes abnormalities in the cerebral cortex structure. Furthermore, chronic high levels of IL-17A in the blood cause a decrease in the activity of microglia, which are important for memory formation. These results suggest that IL-17A is involved in the abnormalities of the central nervous system in autism and psychiatric and neurological disorders.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

IL-17Aが母体免疫活性化による流産や自閉スペクトラム症（ASD）、精神・神経系疾患の発症メカニズムに関与していることが明らかになった。母体のTh17細胞の過剰活性化がIL-17Aを介して流産率を増加させ、IL-17Aが脳内のグリア細胞に異常をもたらすことでASDや精神・神経系疾患の原因となる中枢神経系の異常を引き起こすことが示唆された。これらの発見は、流産やASD、精神・神経系疾患の予防や治療法の開発に繋がる可能性があり、IL-17A抗体などの既存薬の応用や新たな治療薬の開発が期待される。