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Research on control of innate immunity in the small bowel transplantation

Research Project

Project/Area Number 16K20344
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatric surgery
Research InstitutionOsaka University

Principal Investigator

Matsuura Rei  大阪大学, 医学系研究科, 招へい教員 (00747412)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords小腸移植 / 補体 / マクロファージ / 自然免疫 / 移植免疫
Outline of Final Research Achievements

The rejection of the small intestine is usually very severe and represents a significant immunogenic burden to manage. Therefore, the development of a new immunosuppressive drug with a different suppressive mechanism from Calcineurin inhibitors would be desirable in the field of intestinal transplantation. In this study, we demonstrated that PAK-2 inhibitor/PQA-18 suppresses the function of macrophages and induces a clear immunosuppressive effect via a different mechanism from CNI. We found that PQA-18 clearly prolongs the graft survival in a rat intestinal transplant system. PQA-18 can function efficiently in rat immune cells, and in human ones, by virtue of its ability to suppress not only mixed lymphocyte reactions but macrophage differentiation/ polarization in in vitro and in vivo as well. In addition, it can be assumed that PQA-18 is effective in the suppression of T cell activation in the macrophages-independent manner.

Academic Significance and Societal Importance of the Research Achievements

移植後の免疫抑制の方法はこれまでリンパ球に主軸を置いて研究されてきた.現在用いられているリンパ球に対する免疫抑制剤の副作用として,腎障害などが知られている.今回,ラット小腸移植モデルにおよび in vitroの実験において、PQA-18のマクロファージを抑制する効果が示された.PQA-18は自然免疫系細胞の抑制による新たな経路での免疫抑制剤である.今後,投与量や副作用の検証を必要とするが,新たな免疫抑制剤となる可能性が示唆された.

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Human CD200 suppresses the HL-60 mediated xenocytotoxicity.2020

    • Author(s)
      Hiroshi Eguchi, Akira Maeda, Rei Matsuura, Afifah Mod Shabri, Pei-Chi Lo, Tasuku Kodama, Yuki Noguchi, Tomohisa Yoneyama, Chiyoshi Toyama, Yuko Tazuke, Hiroomi Okuyama, Shuji Miyagawa.
    • Journal Title

      Transplant Proc

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The novel immunosuppressant prenylated quinolinecarboxylic acid-18 (PQA-18) suppresses macrophage differentiation and cytotoxicity in xenotransplantation2019

    • Author(s)
      Lo Pei-Chi、Maeda Akira、Kodama Tasuku、Takakura Chihiro、Yoneyama Tomohisa、Sakai Rieko、Noguchi Yuki、Matsuura Rei、Eguchi Hiroshi、Matsunami Katsuyoshi、Okuyama Hiroomi、Miyagawa Shuji
    • Journal Title

      Immunobiology

      Volume: - Issue: 4 Pages: 575-584

    • DOI

      10.1016/j.imbio.2019.04.003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 異種移植におけるヒトCD200の好中球誘導拒絶反応の抑制効果の検討2018

    • Author(s)
      松浦玲
    • Organizer
      第54回日本移植学会総会
    • Related Report
      2018 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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