母体の免疫活性が胎仔の生存と脳の発生に与える影響:IL-17Aとミクログリアの重要な役割
DOI:
https://doi.org/10.51094/jxiv.861キーワード:
自閉スペクトラム症、 インターロイキン17A、 母体免疫活性化、 ミクログリア、 流産抄録
母体免疫活性化(MIA)は、妊娠中の感染症などにより引き起こされる炎症反応であり、流産リスクの増加や胎仔の神経発達障害と関連していることが示唆されている。本総説では、MIAが胎仔の生存と脳発達、特にミクログリアの形質に与える影響について最新の知見を概観する。MIAの研究では、ポリイノシン-ポリシチジル酸(poly(I:C))を用いたマウスモデルが広く使用され、インターロイキン17A(IL-17A)が重要な役割を果たしていることが示されている。IL-17Aは、直接的に、あるいはミクログリアの活性化を介して間接的に、胎児脳の発達に影響を与える可能性がある。RORγt過剰発現マウスを用いた研究では、IL-17Aの慢性的な過剰産生が胎盤の脆弱性を増大させ、poly(I:C)誘導性の流産リスクを高めることが示された。また、IL-17Aの胎児脳室内投与実験により、ミクログリアの活性化と局在変化が引き起こされることが明らかになった。活性化されたミクログリアは、神経前駆細胞の過剰な貪食や異常なシナプス刈り込みを引き起こし、長期的な神経発達に影響を与える可能性がある。これらの知見は、MIAが自閉スペクトラム症(ASD)などの神経発達障害の発症リスクを高める可能性を支持する。今後の研究課題としては、IL-17A以外のサイトカインとの相互作用の解明、ミクログリア活性化の長期的影響の検討、MIAの影響を受けやすい臨界期の特定、ハイリスク妊婦の早期発見などの予防や新規治療法の開発などが挙げられる。研究成果の社会還元に際しては、適切なリスクコミュニケーションと倫理的配慮が不可欠である。MIA研究は、胎仔期の環境が生涯の健康に影響を与えるという観点から、公衆衛生学的にも重要な意義を持つ。今後の研究では、これらの知見をさらに発展させ、DOHaD学説に基づいた予防医学や個別化医療の発展につなげていくことが期待される。
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公開日時: 2024-08-30 00:40:14 UTC
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久保, 明澄
神谷, 沙羅
樋口, 浩輝
中村, 賢佑
岸, 恭子
佐々木, 哲也
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