The role of lipid metabolism in T cell differentiation and function
| Project/Area Number |
18K06923
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Saeki Kazuko 順天堂大学, 医学部, 准教授 (00553273)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | T細胞分化 / 脂質代謝 / 脂肪酸 / マウス病態モデル / CD4陽性T細胞 / ヘルパーT細胞 / 脂質 / 病態モデル / 膜脂質 / T細胞 |
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| Outline of Final Research Achievements |
In this study, we found that naive CD4+ T cells dramatically change their neutral lipid stores and membrane lipid composition during differentiation into helper T cells. Th1 cells highly express glycolytic enzymes and diacylglycerol O-acyltransferase 1, which result in accumulation of neutral lipids generated from glucose. The accumulated neutral lipids may contribute to the maintenance of Th1 cell survival during nutrient starvation. By contrast, regulatory T cells highly express several fatty acid transporters, which result in upregulation of intracellular uptake of fatty acids.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、ヘルパーT細胞が分化過程で代謝のパターンを変化させるという報告が相次いでいるが、その多くが親水性代謝物を中心とした解析で、脂質代謝物の解析は遅れている。本研究では、T細胞の分化により貯蔵脂質の量や細胞膜の飽和度が大きく変化していることを明らかにした。特に、抑制性T細胞が細胞外の脂肪酸を積極的に取り込んでいることが明らかとなり、食に含まれる脂質の質が抑制性T細胞の細胞膜の脂質組成にそのまま反映されることが想定される。近年、いくつかの炎症性疾患は増加傾向にあり、本研究の成果が食餌の欧米化と炎症性疾患の関連性を解く手がかりとなることが期待される。
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Report
(5 results)
Research Products
(30 results)
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[Journal Article] Leukotriene A4 hydrolase deficiency protects mice from diet-induced obesity by increasing energy expenditure through neuroendocrine axis.2020
Author(s)
Uzawa H, Kohno D, Koga T, Sasaki T, Fukunaka A, Okuno T, Jo-Watanabe A, Kazuno S, Miyatsuka T, Kitamura T, Fujitani Y, Watada H, Saeki K*, Yokomizo T
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Journal Title
FASEB J
Volume: 34(10)
Issue: 10
Pages: 13949-13958
DOI
Related Report
Peer Reviewed
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[Journal Article] Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation.2020
Author(s)
Tomoaki Koga, Fumiyuki Sasaki, Kazuko Saeki, Soken Tsuchiya, Toshiaki Okuno, Mai Ohba, Takako Ichiki, Satoshi Iwamoto, Hirotsugu Uzawa, Keiko Kitajima, Chikara Meno, Eri Nakamura, Norihiro Tada, Yoshinori Fukui, Junichi Kikuta, Masaru Ishii, Yukihiko Sugimoto, and Mitsuyoshi Nakao, Takehiko Yokomizo.
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Journal Title
Cellular & Molecular Immunology
Volume: 8
Issue: 6
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Leukotriene B4 promotes neovascularization and macrophage recruitment in murine wet-type AMD models.2018
Author(s)
Sasaki F., Koga T., Ohba M., Saeki K., Okuno T., Ishikawa K., Nakama T., Nakao S., Yoshida S., Ishibashi T., Ahmadieh H., Kanavi M. R., Hafezi-Moghadam A., Penninger J. M., Sonoda K. H., Yokomizo T.
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Journal Title
JCI Insight
Volume: 3
Issue: 18
Pages: 96902-96902
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Deficiency of BLT1, the high-affinity receptor for LTB4, alleviates allergic conjunctivitis in mice.2019
Author(s)
Hirakata T., Lee C. H., Yasukawa K., Adachi K., Saeki K., Okuno T., Murakami A., Matsuda A., Yokomizo T
Organizer
60th ICBL, International Conference on the Bioscience of Lipids
Related Report
Int'l Joint Research
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