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Survey of molecular mechanisms for avoiding rejection focusing on the genetic background of liver allograft

Research Project

Project/Area Number 18K06786
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionKyushu University

Principal Investigator

Tajima Soichiro  九州大学, 大学病院, 薬剤師 (10579460)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords生体肝移植 / 拒絶反応 / 免疫抑制薬 / 個別化医療 / 免疫寛容 / IFN-γ / タクロリムス / 肝移植
Outline of Final Research Achievements

The development of acute rejection after living-donor liver transplantation (LDLT) often results in fatal liver dysfunction. Therefore, immunosuppression induction therapy in LDLT requires stricter control. In order to overcome rejection in post-liver transplantation immunosuppressive therapy, we searched for a novel molecular mechanism focusing on the genetic background of liver allograft. Focusing on IFR as a candidate molecule involved in individual differences in rejection in LDLT patients, we proceeded with analysis using cytotoxic lymphocytes (NK cells) that play a central role in rejection. As a result, the relationship between IFR and cytotoxic activity of NK cells was shown. Therefore, it was suggested that the expression of IFR in liver allograft reduced the cytotoxic activity of NK cells and may be involved in the avoidance of rejection.

Academic Significance and Societal Importance of the Research Achievements

移植直前のドナー肝を用いた遺伝子発現解析により得られた新しい免疫制御因子としてのIFRに着目し、IFRのNK細胞における細胞傷害活性の抑制作用を明らかにした。臨床的にはIFRが新しい作用機序の画期的な免疫抑制薬の標的分子となりうることが示唆され、IFRの免疫学的意義の詳細な解明によって、多方面への波及効果が期待できる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2022 2021 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Development and Validation of A Liquid Chromatography-Tandem Mass Spectrometry Method to Simultaneously Measure Tacrolimus and Everolimus Concentrations in Kidney Allograft Biopsies After Kidney Transplantation2022

    • Author(s)
      Zhang Mengyu、Tajima Soichiro、Shigematsu Tomohiro、Noguchi Hiroshi、Kaku Keizo、Tsuchimoto Akihiro、Okabe Yasuhiro、Egashira Nobuaki、Ieiri Ichiro
    • Journal Title

      Therapeutic Drug Monitoring

      Volume: 44 Issue: 2 Pages: 275-281

    • DOI

      10.1097/ftd.0000000000000912

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Establishment of an experimental rat model of tacrolimus-induced kidney injury accompanied by interstitial fibrosis2021

    • Author(s)
      Fu Rao、Tajima Soichiro、Shigematsu Tomohiro、Zhang Mengyu、Tsuchimoto Akihiro、Egashira Nobuaki、Ieiri Ichiro、Masuda Satohiro
    • Journal Title

      Toxicology Letters

      Volume: 341 Pages: 43-50

    • DOI

      10.1016/j.toxlet.2021.01.020

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neutrophil Gelatinase-Associated Lipocalin Is Not Associated with Tacrolimus-Induced Acute Kidney Injury in Liver Transplant Patients Who Received Mycophenolate Mofetil with Delayed Introduction of Tacrolimus2019

    • Author(s)
      Fukuda Mio、Suetsugu Kimitaka、Tajima Soichiro、Katsube Yurie、Watanabe Hiroyuki、Harada Noboru、Yoshizumi Tomoharu、Egashira Nobuaki、Mori Masaki、Masuda Satohiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 12 Pages: 3103-3103

    • DOI

      10.3390/ijms20123103

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Urinary Human Epididymis Secretory Protein 4 as a Useful Biomarker for Subclinical Acute Rejection Three Months after Kidney Transplantation2019

    • Author(s)
      Tajima Soichiro、Fu Rao、Shigematsu Tomohiro、Noguchi Hiroshi、Kaku Keizo、Tsuchimoto Akihiro、Okabe Yasuhiro、Masuda Satohiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 19 Pages: 4699-4699

    • DOI

      10.3390/ijms20194699

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical prospects of biomarkers for the early detection and/or prediction of organ injury associated with pharmacotherapy2019

    • Author(s)
      Tajima Soichiro、Yamamoto Nanae、Masuda Satohiro
    • Journal Title

      Biochemical Pharmacology

      Volume: 170 Pages: 113664-113664

    • DOI

      10.1016/j.bcp.2019.113664

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Biomarkers for individualized dosage adjustments in immunosuppressive therapy using calcineurin inhibitors after organ transplantation2018

    • Author(s)
      Fu Rao、Tajima Soichiro、Suetsugu Kimitaka、Watanabe Hiroyuki、Egashira Nobuaki、Masuda Satohiro
    • Journal Title

      Acta Pharmacologica Sinica

      Volume: 40 Issue: 2 Pages: 151-159

    • DOI

      10.1038/s41401-018-0070-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Urinary Microtubule-Associated Protein 1 Light Chain 3 and Neutrophil Gelatinase-Associated Lipocalin, as Potential Noninvasive Biomarkers for Subclinical Rejection at 3 Months after kidney Transplantation2019

    • Author(s)
      Soichiro Tajima, Rao Fu, Mio Fukuda, Kimitaka Suetsugu, Yasuhiro Okabe, Satohiro Masuda
    • Organizer
      American Transplant Congress 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Relationship between autophagy and acute rejection after kidney transplant2018

    • Author(s)
      2.Rao Fu, Soichiro Tajima, Kimitaka Suetsugu, Nanae Yamamoto, Yasuhiro Okabe, Satohiro Masuda
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology(WCP2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腎移植患者の急性拒絶反応発現を検出するための新規尿中バイオマーカーの探索2018

    • Author(s)
      1.田島 壮一郎, 付 饒, 末次 王卓, 土本 晃裕, 岡部 安博, 増田 智先
    • Organizer
      第28回日本医療薬学会年会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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