• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Therapeutic approach for unexplained abortion and preterm birth by glycolipid antigens: an immunological perspective

Research Project

Project/Area Number 17K11255
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionNippon Medical School

Principal Investigator

Negishi Yasuyuki  日本医科大学, 医学部, 講師 (50644580)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
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)
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
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Book (2 results)

  • [Journal Article] A combination of check-point blockade and α-galactosylceramide elicits longlasting suppressive effects on murine hepatoma cell growth in vivo2020

    • Author(s)
      Ishii, K, Shimizu, M, Kogo, H, Tamura, H, Negishi, Y, Morita, R, Takahashi, H
    • Journal Title

      Immunobiology

      Volume: 225 Issue: 1 Pages: 151860-151860

    • DOI

      10.1016/j.imbio.2019.10.009

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of tumor-specific CD8+ cytotoxic T lymphocytes from naive human T cells by using Mycobacterium-derived mycolic acid and lipoarabinomannan-stimulated dendritic cells2019

    • Author(s)
      Tomita Y, Watanabe E, Shimizu M, Negishi Y, Kondo Y, Takahashi H
    • Journal Title

      Cancer immunology, immunotherapy

      Volume: 68 Issue: 10 Pages: 1605-1619

    • DOI

      10.1007/s00262-019-02396-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Miscarriage induced by adoptive transfer of dendritic cells and invariant natural killer T cells into mice2018

    • Author(s)
      Negishi Yasuyuki、Ichikawa Tomoko、Takeshita Toshiyuki、Takahashi Hidemi
    • Journal Title

      European Journal of Immunology

      Volume: 48 Issue: 6 Pages: 937-949

    • DOI

      10.1002/eji.201747162

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Innate immune cells in reproduction2018

    • Author(s)
      Negishi Yasuyuki、Takahashi Hidemi、Kuwabara Yoshimitsu、Takeshita Toshiyuki
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 44 Issue: 11 Pages: 2025-2036

    • DOI

      10.1111/jog.13759

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distribution of invariant natural killer T cells and dendritic cells in late pre-term birth without acute chorioamnionitis2017

    • Author(s)
      Negishi, Y. Shima, Y. Takeshita, T. Takahashi, H.
    • Journal Title

      American Journal of Reproductive Immunology

      Volume: - Issue: 6

    • DOI

      10.1111/aji.12658

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 絨毛膜羊膜炎を伴わない原因不明早産の免疫学的解析-無菌性炎症からのアプローチ2019

    • Author(s)
      根岸 靖幸
    • Organizer
      第27回日本胎盤学会 (学会賞(相馬賞)受賞)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Role of innate immune cells in murine and human reproduction2019

    • Author(s)
      Yasuyuki Negishi
    • Organizer
      第14回国際生殖免疫学会(第34回日本生殖免疫学会合同開催)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 免疫学的知見による新しい流早産発症メカニズムの解明2019

    • Author(s)
      根岸 靖幸
    • Organizer
      第47回日本臨床免疫学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 無菌性炎症に起因する流早産発症メカニズムと自然免疫の役割2019

    • Author(s)
      根岸 靖幸
    • Organizer
      第71回日本産科婦人科学会
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
  • [Presentation] Role of dendritic cells and invariant natural killer T cells in glycolipid antigen-induced murine miscarriage2018

    • Author(s)
      根岸 靖幸
    • Organizer
      第47回日本免疫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 糖脂質抗原α-galactosylceramideによって活性化された樹状細胞、invariant natural killer T細胞はマウス流産を引き起こす2018

    • Author(s)
      根岸 靖幸
    • Organizer
      第33回日本生殖免疫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Distribution and kinetics of immune cells in decidua for extreme to moderate preterm births without acute chorioamnionitis2018

    • Author(s)
      根岸 靖幸
    • Organizer
      第24回国際胎盤学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Miscarriage induced by activated innate immune cells in mice2018

    • Author(s)
      根岸 靖幸
    • Organizer
      American-Sino Joint Meeting of Reproductive Immunology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Accumulation of dendritic cells and invariant natural killer T cells in the decidua of late preterm birth without acute chorioamnionitis2017

    • Author(s)
      Yasuyuki Negishi, Yoshio Shima, Toshiyuki Takeshita, Hidemi Takahashi
    • Organizer
      The 37th Annual Meeting of the American Society for Reproductive Immunology
    • Related Report
      2017 Research-status Report
  • [Presentation] Functional difference between decidual dendritic cells in late preterm birth with and without acute chorioamnionitis2017

    • Author(s)
      Yasuyuki Negishi, Yoshio Shima, Hidemi Takahashi, Toshiyuki Takeshita
    • Organizer
      第25回日本胎盤学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Role of innate immune cells in preterm birth and miscarriages induced by sterile inflammation in mice and humans2017

    • Author(s)
      Yasuyuki Negishi, Tomoko Ichikawa, Yoshio Shima, Toshiyuki Takeshita, Hidemi Takahashi
    • Organizer
      第32回日本生殖免疫学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Adoptive transfer of innate immune cells induce murine fetal loss2017

    • Author(s)
      Yasuyuki Negishi, Tomoko Ichikawa, Eri Watanabe, Hikaru Takeshita, Toshiyuki Takeshita, Hidemi Takahashi
    • Organizer
      第46回日本免疫学会
    • Related Report
      2017 Research-status Report
  • [Book] 基礎と臨床の両側面からみた胎盤学2019

    • Author(s)
      日本胎盤学会編集、(担当:分担執筆, 範囲:III章/胎盤をより詳しく知るために(p375-379))
    • Total Pages
      5
    • Publisher
      メジカルビュー社
    • Related Report
      2019 Annual Research Report
  • [Book] 臨床生殖免疫学2018

    • Author(s)
      柴原浩章(編著)
    • Total Pages
      708
    • Publisher
      中外医学社
    • ISBN
      9784498060883
    • Related Report
      2018 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi