Role of membrane gangliosides in T cell development and activation

• Project/Area Number: 25840040
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Tohoku 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: ¥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.

Research Products

• [Journal Article] Distinct selectivity of gangliosides required for CD4+ T and CD8+ T cell activation (2015)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Control of Homeostatic and Pathogenic Balance in Adipose Tissue by Ganglioside GM3 (2015)
  • 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
  • Peer Reviewed
• [Journal Article] Heterogeneity of gangliosides among T cell subsets (2013)
  • 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
  • Peer Reviewed
• [Journal Article] The Physiological Significance of Ganglioside Species Selectively Expressed on Individual T Cell Subsets (2013)
  • 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
  • Peer Reviewed
• [Presentation] Rearrangements of lipid raft constituents during thymocyte development (2014)
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Distinct expression profiles of sphingolipid species diring T cell development (2013)
  • 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
• [Book] Glycoscience: Biology and Medicine (Gangliosides in T cell immunity) (2014)
  • Author(s): Nagafuku, M., Inokuchi, J.
  • Total Pages: 7
  • Publisher: Springer
• [Book] Sugar Chains (Gangliosides and T cell immunity) (2014)
  • Author(s): Nagafuku, M., Inokuchi, J.
  • Total Pages: 20
  • Publisher: Springer