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Immune control by polysaccharides derived from microbes

Research Project

Project/Area Number 16K08737
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionKyoto University

Principal Investigator

Takahara Kazuhiko  京都大学, 生命科学研究科, 准教授 (90301233)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords微生物糖鎖 / 敗血症 / 免疫抑制 / 免疫賦活 / C. albicans / レクチン / IL-10 / IFN-gamma / 糖鎖 / 免疫制御 / ワクチン
Outline of Final Research Achievements

There are 2-3 million of sepsis patients per year in the world. In Japan, we approximately observe 300,000 sepsis patients, leading to 100,000 to150,000 death per year. It is the major treatment of sepsis to suppress the initial inflammation by anti-inflammatory drugs. However, 70% of deaths are caused by hypo-immune responses induced in the late phase of sepsis. In this study, we attempted to identify an immune suppressive mechanism derived a pathogen, and applying it to new treatment of sepsis effective on the early and late phase.
We previously indicated that glycan in surface polysaccharides of opportunistic pathogen, Candida albicans, suppressed the initial inflammation. The we also found that the glycan ameliorate hypo-immune responses in the late phase of sepsis. In the glycan, alpha-mannan moieties in the glycan induced the effects though production of immune suppressive cytokine IL-10.

Academic Significance and Societal Importance of the Research Achievements

申請者は、病原性酵母由来の糖鎖が敗血症を改善する事を見いだした。糖鎖の作用機構を解析する中で、複雑な糖鎖から免疫を制御する蛋白質(IL-10)の産生に働く部分を合成が可能な領域まで絞り込んだ。これにより、今後薬剤としての開発も可能になった。
また、本成果は病原性酵母戦略の一部を明らかにし、これを基に既存の薬剤により効果の認められない慢性化病原性酵母感染症の新たな治療法への開発へと繋がる可能性がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 2016 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Cystine uptake through the cystine/glutamate antiporter xCT triggers glioblastoma cell death under glucose deprivation2017

    • Author(s)
      Goji, T., Takahara, K., Negishi, M. and Katoh, H.
    • Journal Title

      J. Biol. Chem.

      Volume: 292 Issue: 48 Pages: 19721-19732

    • DOI

      10.1074/jbc.m117.814392

    • NAID

      120006482852

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Absence of DCIR1 reduces the rate of endotoxemic hepatitis in mice.2017

    • Author(s)
      Ishiguro T, Fukawa T, Akaki K, Nagaoka K, Takeda T, Iwakura Y ,Inaba K, Takahara K.
    • Journal Title

      Eur J Immunol.

      Volume: 47 Issue: 4 Pages: 704-712

    • DOI

      10.1002/eji.201646814

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Involvement of Dectin-1 in localization γδ T cell in the skin2018

    • Author(s)
      須藤 恒一
    • Organizer
      The 18th International Joint Mini-Symposium on Molecular and Cell Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Amelioration of DSS-induced colitis in DCIR1-deficient mice2016

    • Author(s)
      TAKAHARA Kazuhiko, IWAKURA Yoichiro, INABA Kayo
    • Organizer
      日本免疫学会総会・学術終会
    • Place of Presentation
      沖縄コンベンションセンター
    • Related Report
      2016 Research-status Report
  • [Book] 臨床免疫・アレルギー科(C型レクチンによる生体応答制御-恒常性の維持と応用-)2016

    • Author(s)
      高原 和彦
    • Total Pages
      7
    • Publisher
      科学評論社
    • Related Report
      2016 Research-status Report
  • [Remarks] 京都大学 生命科学研究科 高次生命科学専攻 生体応答学分野

    • URL

      http://zoo.zool.kyoto-u.ac.jp/imm/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都大学生命科学研究科高次生命科学専攻生体応答学分野

    • URL

      http://zoo.zool.kyoto-u.ac.jp/imm/

    • Related Report
      2017 Research-status Report
  • [Remarks] 京都大学生命科学研究科高次生命科学専攻体制統御学講座生体応答分野

    • URL

      http://zoo.zool.kyoto-u.ac.jp/imm/

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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