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The role of lipid metabolism in T cell differentiation and function

Research Project

Project/Area Number 18K06923
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionJuntendo University

Principal Investigator

Saeki Kazuko  順天堂大学, 医学部, 准教授 (00553273)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
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)
KeywordsT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
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.

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。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 6 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] Shanghai Jiao Tong Univ Sch of Med(中国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Shahid Beheshti Univ of Med Sciences(イラン)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Harvard Medical School(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] IMBA(オーストリア)

    • Related Report
      2018 Research-status Report
  • [Journal Article] A Western Diet Alters Skin Ceramides and Compromises the Skin Barrier in Ears2022

    • Author(s)
      Tan Kahbing Jasmine、Nakamizo Satoshi、Lee-Okada Hyeon-Cheol、Sato Reiko、Chow Zachary、Nakajima Saeko、Common John E.A.、Saeki Kazuko、Yokomizo Takehiko、Ginhoux Florent、Kabashima Kenji
    • Journal Title

      Journal of Investigative Dermatology

      Volume: - Issue: 7 Pages: 2020-2023.e2

    • DOI

      10.1016/j.jid.2021.12.017

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The c‐terminal region of BLT2 restricts its localization to the lateral membrane in a LIN7C‐dependent manner2021

    • Author(s)
      Hara Takuya、Saeki Kazuko、Jinnouchi Hiromi、Kazuno Saiko、Miura Yoshiki、Yokomizo Takehiko
    • Journal Title

      The FASEB Journal

      Volume: 35 Issue: 2 Pages: 21364-21364

    • DOI

      10.1096/fj.202002640r

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Up-regulation of cytosolic prostaglandin E synthase in fetal-membrane and amniotic prostaglandin E2 accumulation in labor2021

    • Author(s)
      Nanase Takahashi, Toshiaki Okuno, Hiroki Fujii, Shintaro Makino, Masaya Takahashi, Mai Ohba, Kazuko Saeki, Atsuo Itakura, Satoru Takeda, Takehiko Yokomizo
    • Journal Title

      PLoS One

      Volume: 16 Issue: 4 Pages: e0250638-e0250638

    • DOI

      10.1371/journal.pone.0250638

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leukotriene B4 receptor type 2 (BLT2) accelerates the healing of intestinal lesions by promoting epithelial cell proliferation2020

    • Author(s)
      Matsumoto Y, Matsuya Y, Kano N, Amagase K, Saeki K, Matsumoto K, Yokomizo T, Kato S
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics

      Volume: 373 Issue: 1 Pages: 1-9

    • DOI

      10.1124/jpet.119.263145

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [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
    • Journal Title

      FASEB J

      Volume: 34(10) Issue: 10 Pages: 13949-13958

    • DOI

      10.1096/fj.202001148r

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Cellular & Molecular Immunology

      Volume: 8 Issue: 6 Pages: 1-13

    • DOI

      10.1038/s41423-020-00559-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dietary omega-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses.2019

    • Author(s)
      Hirakata T., Lee H. C., Ohba M., Saeki K., Okuno T., Murakami A., Matsuda A., Yokomizo T.
    • Journal Title

      FASEB J

      Volume: 33 Issue: 3 Pages: 3392-3403

    • DOI

      10.1096/fj.201801805r

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leukotriene B4 receptor 2 regulates the proliferation migration and barrier integrity of bronchial epithelial cells2018

    • Author(s)
      M Liu J Shen H Yuan F Chen H Song H Qin Y Li J Xu Q Ye S Li K Saeki T Yokomizo
    • Journal Title

      J Cell Physiol

      Volume: 印刷中 Issue: 8 Pages: 6117-6124

    • DOI

      10.1002/jcp.26455

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Profiling of bioactive lipids in different dendritic cell subsets using an improved multiplex quantitative LC-MS/MS method.2018

    • Author(s)
      Ohba M., Saeki K., Koga T., Okuno T., Kobayashi Y., Yokomizo T.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 504 Issue: 3 Pages: 562-568

    • DOI

      10.1016/j.bbrc.2018.06.026

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      JCI Insight

      Volume: 3 Issue: 18 Pages: 96902-96902

    • DOI

      10.1172/jci.insight.96902

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 生理活性脂質ロイコトリエンB4とその受容体による免疫調節機構2018

    • Author(s)
      古賀友紹, 佐伯和子, 横溝岳彦
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 70

    • Related Report
      2018 Research-status Report
  • [Presentation] Protective roles of leukotriene B4 receptor type 2 on pore forming toxin-induced cell membrane damage.2021

    • Author(s)
      遅源, 佐伯和子, 横溝岳彦
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Leukotriene B4 receptor type 2 enhances cell membrane repair and protects cell death caused by pore forming agent.2021

    • Author(s)
      遅源, 佐伯和子, 横溝岳彦
    • Organizer
      第8回日本細胞外小胞学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 高度不飽和脂肪酸の合成系と局所における役割 (シンポジウム)2020

    • Author(s)
      李賢哲, 李慶賢, 佐伯和子, 横溝岳彦
    • Organizer
      第93回日本生化学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 食餌誘導性肥満におけるロイコトリエンA4水解酵素の役割2020

    • Author(s)
      鵜澤博嗣, 佐伯和子, 古賀友紹, 綿田裕孝, 横溝岳彦
    • Organizer
      第93回日本生化学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 代謝におけるロイコトリエンA4水解酵素の役割の解析2019

    • Author(s)
      鵜澤博嗣, 古賀友紹, 佐伯和子, 奥野利明, 綿田裕孝, 横溝岳彦
    • Organizer
      第92回日本生化学会
    • Related Report
      2019 Research-status Report
  • [Presentation] The role of leukotriene A4 hydrolase in metabolism.2019

    • Author(s)
      Uzawa H., Saeki K., Koga T., Okuno T., Miyatsuka T., Watada H., Yokomizo T
    • Organizer
      60th ICBL, International Conference on the Bioscience of Lipids
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Protective roles of leukotriene B4 receptor type 2 in pneumolysin-induced epithelial injury.2019

    • Author(s)
      Chi Y., Saeki K., Yokomizo T
    • Organizer
      60th ICBL, International Conference on the Bioscience of Lipids
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Spatiotemporal regulation of novel DC subsets by LTB4-BLT1 signaling.2019

    • Author(s)
      Koga T., Sasaki F., Saeki K., Okuno T., Nakao M., Yokomizo T
    • Organizer
      60th ICBL, International Conference on the Bioscience of Lipids
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [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
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] アレルギー性結膜炎におけるオメガ3脂肪酸の効果の検証2018

    • Author(s)
      平形寿彬, 李賢哲, 大塲麻衣, 佐伯和子, 奥野利明, 松田彰, 村上晶, 横溝岳彦
    • Organizer
      第60回日本脂質生化学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ロイコトリエンA4水解酵素の代謝における解析2018

    • Author(s)
      鵜澤博嗣, 古賀友紹, 奥野利明, 佐伯和子, 横溝岳彦
    • Organizer
      第60回日本脂質生化学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 生理活性脂質12-HHTのBLT2受容体を介した生体保護的役割2018

    • Author(s)
      佐伯和子, 重松美沙子, 古賀友紹, 奥野利明, 横溝岳彦
    • Organizer
      第91回日本生化学会 シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] 別冊BIO Clinica 慢性炎症と疾患 特集「皮膚疾患と慢性炎症」皮膚の創傷治癒と恒常性維持を担う生理活性脂質2021

    • Author(s)
      佐伯和子、石井由美子、劉珉、横溝岳彦
    • Total Pages
      5
    • Publisher
      北隆館
    • Related Report
      2021 Annual Research Report
  • [Remarks] 順天堂大学医学部生化学第一講座

    • URL

      http://plaza.umin.ac.jp/j_bio/

    • Related Report
      2021 Annual Research Report 2020 Research-status Report 2019 Research-status Report
  • [Remarks] http://plaza.umin.ac.jp/j_bio/index.html

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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