New therapeutic strategies for miscarriage and preterm birth by regulation of innate immunity

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09679
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nippon Medical School
• Principal Investigator: Negishi Yasuyuki 日本医科大学, 医学部, 准教授 (50644580)
• Co-Investigator(Kenkyū-buntansha): 桑原 慶充 日本医科大学, 医学部, 准教授 (40373013)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 早産 / 流産 / 自然免疫 / 無菌性炎症 / マクロファージ / 樹状細胞 / NKT細胞 / HMGB1

Outline of Final Research Achievements

In the study, we revealed that excessive activation of cells belonging to the innate immune system, such as macrophages, dendritic cells, and natural killer T (NKT) cells in the placenta, may be the triggers or exacerbating factors for onset of preterm birth and miscarriage. The study also suggested that the release of damage associated molecular patterns (DAMPs) called high-mobility group box-1 (HMGB1) is important for triggering the inflammation. In addition, we found that progesterone and heparin are effective in controlling excessive inflammation, which is mainly caused by activation of innate immunity. Based on these results, we propose a novel mechanism of preterm birth. We expect further developments in the prevention of preterm birth in the future.

Free Research Field

生殖免疫学

Academic Significance and Societal Importance of the Research Achievements

早産は日常診療で最も多く遭遇する産科合併症である。これまで病原体感染に起因する絨毛膜羊膜炎はその主要な原因と考えられてきたが、最近明らかな病原体感染を伴わない早産が意外にも多いことが指摘され、これらは原因不明に分類せざるを得ない。さらに早産の治療法には塩酸リトドリンやマグネシウム製剤などの子宮収縮抑制剤、抗菌薬、安静などが行われるものの、その有効性に関しては流動的であり、特に免疫学的観点からのアプローチはほとんどなされていない。本研究成果はこの原因不明早産の新たなメカニズム提唱と免疫学的治療作用点の発見をもたらすものであり、社会的意義は大きいと考える。