| Project/Area Number |
17K11255
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 早産 / 流産 / 自然免疫 / 無菌性炎症 / 樹状細胞 / iNKT細胞 / プロゲステロン / α-galactosylceramide / 生殖免疫学 / 産婦人科学 / 免疫学 |
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| Outline of Final Research Achievements |
The aim of this study was to analyze the mechanism of unexplained miscarriage and preterm birth (PB), and to explore the therapeutic approach for these diseases by applying glycolipid antigens. In this study, analysis of murine abortion induced by α-GalCer and human decidua obtained from PB was performed.
Although we could not find out the therapeutically effective glycolipid antigen for miscarriage and PB, we confirmed that the dendritic cells and iNKT cells activated by glycolipid antigen could directly induced murine miscarriage. In addition, these activated innate immune cells were found in human decidua obtaimed from PB without chorioamnionitis. It was also found that therapeutic site of progesterone and heparin is related to the modulation of antigen presenting cell.
Collectively, we pointed out the importance of sterile inflammation induced by innate immune cells and alarmins for the unexplained miscarriage and PB.
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| Academic Significance and Societal Importance of the Research Achievements |
人口構成の偏在化が進む我が国に於いて、妊娠・出産率の向上は喫緊の課題であり、不育症、早産などの疾患に対する生殖・産科医療の担う役割は大きい。本研究では、病原体感染が関与せずこれまで原因不明に分類せざるを得なかった流早産には、自然免疫の活性化に起因する無菌性炎症および内因性抗原が重要な役割を果たすことが示された。さらに既存薬剤のプロゲステロンやヘパリンは自然免疫細胞、特に抗原提示細胞に作用する可能性が見いだされ、これら薬剤の抗炎症作用という新たな機能の発見に繋がった。本研究により原因不明流早産のメカニズムの一端が解明され、胎盤内無菌性炎症の制御といった新しい治療概念構築に貢献したと考える。
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