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Role of membrane gangliosides in T cell development and activation

Research Project

Project/Area Number 25840040
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionTohoku Pharmaceutical University

Principal Investigator

NAGAFUKU Masakazu  東北薬科大学, 薬学部, 助教 (20399976)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsガングリオシド / T細胞分化 / TCR / 胸腺 / 糖鎖 / T細胞 / 胸腺細胞 / ラフト / T細胞受容体 / スフィンゴ脂質
Outline of Final Research Achievements

T cell development depends on appropriate signals mediated by T cell receptors and many other receptors. Sphingolipids (gangliosides and sphingomyelin) are thought to form a platform (lipid raft) for receptor-mediated signaling.
We determined the expression profiles of gangliosides during T cell development. Ganglioside levels were greatly increased during the DN3 stage, which was coincidentally with TCRb chain expression. To determine the role of gangliosides in T cell development we prepared GM3S and GM2/GD2S double deficient mice (DKO mice) which don’t express any ganglioside species. DKO mice exhibited abnormal thymic development and greatly reduced in thymocytes. T cell development in DKO mice was arrested at the DN3 stage where TCRb chain gene arrangement occurs. These results suggest unique rafts are formed in the plasma membrane during T cell development and these rafts provide the appropriate distinct intracellular signaling events for successful differentiation.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (14 results)

All 2015 2014 2013

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) Book (2 results)

  • [Journal Article] Distinct selectivity of gangliosides required for CD4+ T and CD8+ T cell activation2015

    • Author(s)
      Inokuchi, J., Nagafuku, M., Ohno, I., Suzuki, A.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1851 Issue: 1 Pages: 98-106

    • DOI

      10.1016/j.bbalip.2014.07.013

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Control of Homeostatic and Pathogenic Balance in Adipose Tissue by Ganglioside GM32015

    • Author(s)
      Nagafuku, M., Sato, T., Sato, S., Shimizu, K., Taira, T., Inokuchi, J.
    • Journal Title

      Glycobiology

      Volume: 25 Issue: 3 Pages: 303-318

    • DOI

      10.1093/glycob/cwu112

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity of gangliosides among T cell subsets2013

    • Author(s)
      Jin-ichi Inokuchi
    • Journal Title

      Cell Mol Life Sci

      Volume: 70 Issue: 17 Pages: 2000-2008

    • DOI

      10.1007/s00018-012-1208-x

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Physiological Significance of Ganglioside Species Selectively Expressed on Individual T Cell Subsets2013

    • Author(s)
      永福 正和,井ノ口 仁一
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 25 Issue: 144 Pages: 159-169

    • DOI

      10.4052/tigg.25.159

    • NAID

      130004841373

    • ISSN
      0915-7352, 1883-2113
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Rearrangements of lipid raft constituents during thymocyte development2014

    • Author(s)
      永福正和、豊島かおる、井ノ口仁一
    • Organizer
      第43回日本免疫学会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] ガングリオシドは腸管におけるNPC1L1を介したコレステロール吸収を制御する2014

    • Author(s)
      二瓶 渉, 永福 正和, 菊地 唯, 井ノ口 仁一
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] マクロファージは内臓脂肪細胞のスフィンゴ糖脂質発現を制御し、脂肪細胞の生理的分化成熟と肥満によるインスリン抵抗性を制御している2014

    • Author(s)
      井ノ口 仁一、永福 正和
    • Organizer
      第56回日本脂質生化学会
    • Place of Presentation
      近畿大学東大阪キャンパス(大阪府東大阪市)
    • Year and Date
      2014-06-06 – 2014-06-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] T細胞分化におけるスフィンゴ脂質の発現制御2013

    • Author(s)
      永福正和、井ノ口仁一
    • Organizer
      第8回スフィンゴテラピー研究会
    • Place of Presentation
      石川県加賀市
    • Related Report
      2013 Research-status Report
  • [Presentation] マクロファージは内臓脂肪細胞のガングリオシド発現を時間的・空間的に支配することにより分化成熟とインスリンシグナルを制御している2013

    • Author(s)
      井ノ口仁一、永福正和
    • Organizer
      第32回日本糖質学会
    • Place of Presentation
      大阪市
    • Related Report
      2013 Research-status Report
  • [Presentation] マクロファージによる内臓脂肪細胞のガングリオシド発現の病態生理学的意義2013

    • Author(s)
      井ノ口仁一、永福正和
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] T細胞分化制御機構および免疫疾患におけるスフィンゴ糖脂質発現の意義2013

    • Author(s)
      永福正和、大野勲、鈴木明身、井ノ口仁一
    • Organizer
      第11回糖鎖科学コンソーシアムシンポジウム
    • Place of Presentation
      仙台市
    • Related Report
      2013 Research-status Report
  • [Presentation] Distinct expression profiles of sphingolipid species diring T cell development2013

    • Author(s)
      永福正和、井ノ口仁一
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      千葉市
    • Related Report
      2013 Research-status Report
  • [Book] Glycoscience: Biology and Medicine (Gangliosides in T cell immunity)2014

    • Author(s)
      Nagafuku, M., Inokuchi, J.
    • Total Pages
      7
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Book] Sugar Chains (Gangliosides and T cell immunity)2014

    • Author(s)
      Nagafuku, M., Inokuchi, J.
    • Total Pages
      20
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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