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A novel immunosuppresive therapy by Type 1 regulatory T cells after lung transplantation

Research Project

Project/Area Number 18K08777
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55040:Respiratory surgery-related
Research InstitutionTohoku University

Principal Investigator

Hisashi Oishi  東北大学, 大学病院, 助教 (60451580)

Co-Investigator(Kenkyū-buntansha) 松田 安史  藤田医科大学, 医学部, 准教授 (00455833)
野田 雅史  東北大学, 大学病院, 講師 (70400356)
岡田 克典  東北大学, 加齢医学研究所, 教授 (90323104)
兼平 雅彦  山梨大学, 大学院総合研究部, 准教授 (90374941)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords肺移植 / 慢性移植肺機能不全 / Type 1 regulatory T 細胞 / CTLA4-Ig / Lymphoid neogenesis / CLAD / Type 1 regulatory T細胞 / 免疫抑制療法 / 拒絶反応
Outline of Final Research Achievements

We investigated the potential of a therapy for chronic lung allograft dysfunction (CLAD) using Type 1 regulatory T (Tr1) cells, which is one of a subset of regulatory T cells. We examined the effect of CTLA4-Ig in a mouse intrapulmonary tracheal transplant model, which is an established animal model of CLAD. CTLA4-Ig was reported to induce Tr1 cells. It was clarified that the fibrous occlusion in the transplanted trachea was significantly suppressed, and the effect of inhibiting CLAD by CTLA4-Ig was shown.

Academic Significance and Societal Importance of the Research Achievements

本研究は肺移植後の慢性期予後に重大な影響を及ぼす慢性移植肺機能不全(Chronic lung allograft dysfunction: CLAD)の治療や予防として、CTLA4-Ig製剤が有効である可能性を示した。現在の医療では、CLADに対する確立した治療法はなく、本研究成果は肺移植医療に大きなインパクトを与えると考える。さらに、CTLA4-Ig製剤はすでに慢性関節リウマチに対しては、国内で承認されている薬剤であり、CLADの治療法としても、臨床応用に非常に近い状態にあるといえる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2021 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Effect of CTLA4-Ig on obliterative bronchiolitis in a mouse intrapulmonary tracheal transplantation model2021

    • Author(s)
      Yamato Suzuki, Hisashi Oishi, Masahiko Kanehira, Yasushi Matsuda, Takashi Hirama, Masafumi Noda, Yoshinori Okada.
    • Journal Title

      Annals of Thoracic and Cardiovascular Surgery

      Volume: In press

    • NAID

      130008131277

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 肺移植後閉塞性細気管支モデルに対するCTLA4-Igの繊維性閉塞抑制効果の検討-マウス肺内気管移植モデルを用いて-2020

    • Author(s)
      鈴木大和, 大石久,兼平雅彦, 渡辺有為, 野津田泰嗣, 平間崇, 鈴木隆哉, 松田安史, 野田雅史, 舟橋淳一, 桜田晃, 岡田克典
    • Organizer
      第36回日本肺および心肺移植研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] CTLA4-Ig Therapy Attenuates Bronchiolitis Obliterans after Mouse Intrapulmonary Trachial Transplantation Model through Possibility of Effect of LAG3+Tregs2019

    • Author(s)
      Y. Suzuki, H. Oishi, M. Kanehira, Y. Matsuda, T. Sado, M. Noda, J. Funahashi, A. Sakurada, Y. Okada.
    • Organizer
      ISHLT 2019 Annual Meeting and Scientific Sessions
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウス肺内気管移植モデルにおけるCTLA4-Igによる気管の線維性閉塞抑制効果の検討2019

    • Author(s)
      2.鈴木大和, 大石 久, 兼平雅彦, 松田安史, 佐渡 哲, 野田雅史, 桜田 晃, 岡田克典
    • Organizer
      第 35回日本肺および心肺移植研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウス肺内気管移植モデルにおけるCTLA4-Igによる気管の線維性閉塞抑制効果の検討2019

    • Author(s)
      鈴木大和、大石 久、兼平雅彦、松田安史、佐渡 哲、野田雅史、舟橋淳一、桜田 晃、岡田克典
    • Organizer
      第35回日本肺および心肺移植研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] CTLA4-Ig attenuates fibrous airway obliteration in a mouse intrapulmonary tracheal transplantation model2019

    • Author(s)
      Yamato Suzuki, Hisashi Oishi, Masahiko Kanehira, Yasushi Matsuda, Tetsu Sado, Masafumi Noda, Jun-ichi Funahashi, Akira Sakurada, Yoshinori Okada
    • Organizer
      The international society for heart and lung transplantation 39th annual meeting and scientific sessions
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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