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Study of antigen-specific immunosuppressive therapy using tolerogenic dendritic cells induced by protein kinase C inhibitor

Research Project

Project/Area Number 17K16208
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Collagenous pathology/Allergology
Research InstitutionEhime University

Principal Investigator

Matsumoto Takuya  愛媛大学, 医学部附属病院, 講師(病院教員) (70724780)

Project Period (FY) 2017-04-01 – 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 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords免疫寛容樹状細胞 / Cキナーゼ阻害剤 / 制御性T細胞 / Cキナーゼ阻害剤 / T細胞エピトープ
Outline of Final Research Achievements

Human tolerogenic dendritic cells(tDCs) can be generated ex vivo from DC precursors using various compounds. We previously reported that DCs treated with conventional protein kinase C inhibitor had potent immunogenic tolerance properties. In addition, PKCI-tCDs might be more useful for inducing therapeutic immunotolerance. The functional characteristics of PKCI is good for making clinical grade tDCs, compared to other compounds. And, we confirmed that we could generate PKCI-tDCs from rheumatoid arthritis or Sjogren’s syndrome patients.
In addition, miRNA array were performed with total RNA exracted from immature DCs, mature DCs, and PKCI-tDCs, to find functional differences of these types of DCs.As a result, we found highly expression of 12 types of miRNA in PKCI-tDCs to compared with other DCs. Functional analysis of these miRNA transducted in DCs are still going.

Academic Significance and Societal Importance of the Research Achievements

樹状細胞は1973年に新しい免疫担当細胞として報告されて以来、獲得免疫のみならず免疫寛容においても重要な役割を果たしていることが報告されている。本研究の特色としてCキナーゼ阻害薬によって誘導されたヒト免疫寛容樹状細胞(tDCs)が、臨床応用の可能性が十分あるということを示し、実臨床の患者においてもtDCsが誘導できることを証明した。また、miRNAを解析することで、今後これらの研究をさらに発展させ、抑制機能を持ったTregsやtDCsを効率よく、安定的に誘導する方法を確立し、膠原病などの自己免疫疾患などの臨床に応用を目指している。

Report

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

    (6 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Mechanisms of tolerance induction by dendritic cells in vivo.2018

    • Author(s)
      Hasegawa H, Matsumoto T
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 350-350

    • DOI

      10.3389/fimmu.2018.00350

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cキナーゼ阻害剤で誘導されたヒト免疫寛容樹状細胞による自己免疫疾患への展開2017

    • Author(s)
      松本卓也,長谷川均
    • Journal Title

      アレルギーの臨床

      Volume: 37(13) Pages: 49-54

    • Related Report
      2017 Research-status Report
  • [Presentation] ANCA関連血管炎の寛解導入および寛解維持期における疾患活動性マーカーとしての血清TIMP1値の有用性の検討2019

    • Author(s)
      石崎淳、松本卓也、末盛浩一郎、佐田榮司、長谷川均、竹中克斗
    • Organizer
      日本リウマチ学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 当院におけるANCA関連血管炎性中耳炎(OMAAV)の臨床的検討2019

    • Author(s)
      末盛浩一郎、石崎淳、松本卓也、佐田榮司、竹中克斗、長谷川均
    • Organizer
      日本リウマチ学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Cキナーゼ阻害剤で誘導されたヒト寛容型樹状細胞の特徴と自己免疫疾患からの誘導2018

    • Author(s)
      長谷川均、松本卓也、石崎淳、末盛浩一郎
    • Organizer
      第62回日本リウマチ学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Characterization of human tolerogenic dendritic cells generated with protein kinase C inhibitor and induction from patients with autoimmune diseases.2017

    • Author(s)
      Hasegawa, H., Matsumoto, T., Adnan, E., Ishizaki, J., Suemori, K., Yasukawa, M.
    • Organizer
      2017 ACR/ARHP Annual Meeting.San Diego, U.S.A. 2017.11.6.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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

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