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Functional elucidation of two forms of Galectin-9 and their potential application to diagnosis

Research Project

Project/Area Number 21K07068
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionKagawa University

Principal Investigator

Niki Toshiro  香川大学, 医学部, 助教 (40558508)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsガレクチン9 / エクソソーム / ガレクチン / ソーティング / 免疫調節 / 細胞外小胞 / レクチン
Outline of Research at the Start

ガレクチン9(Gal-9)は免疫チェックポイント因子かつDAMPs として機能するレクチンである。応募者は1)Extracellular vesicles に内包されたEV Gal-9 と遊離型 Gal-9 の存在、2)それら二形態の分泌の細胞種による差、3)EV Gal-9 と別因子の結合と、それが EVへの Sorting に関連している可能性、4)デング熱患者で血漿中 EV Gal-9 が回復期に上昇すること、を見出した。本研究では二形態の Gal-9 が存在する理由を問うべく、それらの機能、EV への Sorting 機序および EV Gal-9 測定の臨床応用可能性について検討する。

Outline of Final Research Achievements

Human acute monocytic leukemia cell THP1 was shown to secrete Gal-9 encapsulated in exosome-containing extracellular vesicles (EVs) upon PMA stimulation. This Gal-9 was completely encapsulated in EVs and was the L- and M-type splicing variant of Gal-9. An ELISA method for the quantification of EV Gal-9 was developed, and plasma from patients with various diseases was assayed. Since EV Gal-9 was elevated in dengue fever patients during the convalescence period, confirmation by increasing the number of samples is necessary. No differences were observed in AIDS, tuberculosis, and AIDS/tuberculosis, reflecting the severity of the disease.

Academic Significance and Societal Importance of the Research Achievements

Gal-9は複数のリセプターに結合して多機能な作用を及ぼす免疫調節因子であり、ガン免疫療法のターゲットとしても注目されている。一方でDamage-associated molecular patternとしての一面もあり様々な感染症や慢性疾患で血中濃度が顕著に上昇するため疾患の重症度マーカーとしての研究も数多い。本科研費研究ではGal-9にEVに内包された形態が存在していることを示し、その定量方法を開発した。今後様々な疾患の診断、EV内包の分子機序解明およびGal-9抑制薬の開発等において新しい視点を与える重要な研究成果である。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (11 results)

All 2023 2022 Other

All Int'l Joint Research (8 results) Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results)

  • [Int'l Joint Research] Weill Cornell Medicine/UCSF/Vitalant(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Gustave Roussy(フランス)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University Medical Center Groningen(オランダ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] コーネル大学/UCSF/Vitalant(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Gustave Roussy(フランス)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] グローニンゲン大学(オランダ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] コーネル大学/UCSF/Vitalant(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Gustave Roussy(フランス)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Plasma N‐Cleaved Galectin‐9 Is a Surrogate Marker for Determining the Severity of COVID‐19 and Monitoring the Therapeutic Effects of Tocilizumab2023

    • Author(s)
      Hozumi H, Maeda Y, Niki T, Chagan-Yasutan H, Bai G, Matsuba T, Furushima D, Ashino y, Hattori T
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 24 Issue: 4 Pages: 3591-3591

    • DOI

      10.3390/ijms24043591

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human galectin-9 potently enhances SARS-CoV-2 replication and inflammation in airway epithelial cells2023

    • Author(s)
      Du Li、Bouzidi Mohamed S、Gala Akshay、Deiter Fred、Billaud Jean-Noel、Yeung Stephen T、Dabral Prerna、Jin Jing、Simmons Graham、Dossani Zain Y、Niki Toshiro、Ndhlovu Lishomwa C、Greenland John R、Pillai Satish K
    • Journal Title

      Journal of Molecular Cell Biology

      Volume: 15 Issue: 4 Pages: 1-14

    • DOI

      10.1093/jmcb/mjad030

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Galectin-9 protects humanized-ACE2 immunocompetent mice from SARS-CoV-2 infection2022

    • Author(s)
      Yeung Stephen T.、Premeaux Thomas A.、Du Li、Niki Toshiro、Pillai Satish K.、Khanna Kamal M.、Ndhlovu Lishomwa C.
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 1011185-1011185

    • DOI

      10.3389/fimmu.2022.1011185

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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