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Development of a novel corneal transplant immunotolerance therapy using anti-CD80/86 antibody-induced regulatory T cells

Research Project

Project/Area Number 18K16935
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionJuntendo University

Principal Investigator

Inomata Takenori  順天堂大学, 医学部, 准教授 (10645667)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords角膜移植免疫 / 免疫寛容 / 抗CD80/86抗体 / 拒絶反応 / 制御性T細胞 / 角膜移植 / 移植免疫 / 誘導性制御性T細胞 / 血管新生 / ハイリスク角膜移植
Outline of Final Research Achievements

In this study, we used a mouse high-risk corneal transplant model that induced neovascularization, investigated the mechanism of immunosuppressive effect of anti-CD80/86 antibody on corneal grafts for developing a new immune tolerance induction therapy in corneal transplantation. The administration of anti-CD80/86 antibody revealed a Th1-dominant immunosuppressive effect. Furthermore, the effect of reducing inflammatory cytokines was clarified from MLR. These may enable novel immunosuppressive therapy with anti-CD80/86 antibody.

Academic Significance and Societal Importance of the Research Achievements

角膜移植後の急性拒絶反応に対して、ステロイドやタクロリムスなどの免疫抑制剤を中心とした治療が行われているが、感染症、自己免疫疾患の合併、再移植などで血管新生を生じたハイリスク症例では未だにその40-90%に高い拒絶反応を伴う。本邦においてはドナー角膜が充足しているとは言えず、移植臓器において長期的に免疫寛容(免疫抑制剤を中止しても移植臓器が十分に機能する状態)が成立することが臨床的に重要である。本研究から抗CD80/86抗体投与により、Th1優位の免疫抑制効果が明らかになった。これらの結果は抗CD80/86抗体を用いた新規免疫抑制療法開発の基盤となる。

Report

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

    (11 results)

All 2020 2018

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Variable Responses to Corneal Grafts: Insights from Immunology and Systems Biology2020

    • Author(s)
      Di Zazzo Antonio、Lee Sang-Mok、Sung Jaemyoung、Niutta Matteo、Coassin Marco、Mashaghi Alireza、Inomata Takenori
    • Journal Title

      Journal of Clinical Medicine

      Volume: 9 Issue: 2 Pages: 586-586

    • DOI

      10.3390/jcm9020586

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulatory T Cell Modulation of Cytokine and Cellular Networks in Corneal Graft Rejection2018

    • Author(s)
      Tahvildari Maryam、Inomata Takenori、Amouzegar Afsaneh、Dana Reza
    • Journal Title

      Current Ophthalmology Reports

      Volume: 6 Issue: 4 Pages: 266-274

    • DOI

      10.1007/s40135-018-0191-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Method for selective quantification of immune and inflammatory cells in the cornea using flow cytometry2018

    • Author(s)
      Ogawa Mamoru、Inomata Takenori、Shiang Tina、Tsubota Kazuo、Murakami Akira
    • Journal Title

      Journal of Biological Methods

      Volume: 5 Issue: 4 Pages: 1-1

    • DOI

      10.14440/jbm.2018.237

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pathological conversion of regulatory T cells is associated with loss of allotolerance2018

    • Author(s)
      Hua Jing、Inomata Takenori、Chen Yihe、Foulsham William、Stevenson William、Shiang Tina、Bluestone Jeffrey A.、Dana Reza
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 7059-7059

    • DOI

      10.1038/s41598-018-25384-x

    • Related Report
      2018 Research-status Report
  • [Journal Article] The immunoregulatory role of corneal epithelium-derived thrombospondin-1 in dry eye disease2018

    • Author(s)
      Tan Xuhua、Chen Yihe、Foulsham William、Amouzegar Afsaneh、Inomata Takenori、Liu Yizhi、Chauhan Sunil K.、Dana Reza
    • Journal Title

      The Ocular Surface

      Volume: 16 Issue: 4 Pages: 470-477

    • DOI

      10.1016/j.jtos.2018.07.005

    • Related Report
      2018 Research-status Report
  • [Presentation] Blockade of CD80/86 prolongs corneal allograft survival2020

    • Author(s)
      Yuichi Okumura, Takenori Inomata, Keiichi Fujimoto, Koichiro Uchida, Tina Shiang, Akira Murakami
    • Organizer
      Gordon Research Conference on Cornea and Ocular Surface Biology and Pathology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Blockade of CD80/86 prolongs corneal allograft survival2020

    • Author(s)
      Okumura Y, Inomata T, Fujimoto K, Uchida K, Shiang T, Murakami A
    • Organizer
      Gordon Research Conference on Cornea and Ocular Surface Biology and Pathology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗CD80/86抗体の角膜移植における免疫学的効果の検討2018

    • Author(s)
      藤本啓一, 猪俣武範, 内田浩一郎, Tina Shiang, 村上晶
    • Organizer
      角膜カンファランス2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 制御性T細胞を用いた角膜移植における新規免疫抑制療法開発のための研究2018

    • Author(s)
      猪俣 武範
    • Organizer
      角膜カンファランス2018
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 抗CD80/86抗体のマウス角膜移植における制御性T細胞への影響の検討2018

    • Author(s)
      藤本啓一、猪俣武範、内田浩一郎、奥村雄一、村上晶
    • Organizer
      第122回日本眼科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] The effect of Anti-CD80/86 antibody on regulatory T cells in murine corneal transplantation2018

    • Author(s)
      Keiichi Fujimoto, Takenori Inomata, Koichiro Uchida, Tina Shiang, Yuichi Okumura, Akira Murakami
    • Organizer
      ARVO 2018 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-03-23  

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