Determination of helper T cell fate by amino acid metabolism

• Project/Area Number: 15K15155
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Ehime University
• Principal Investigator: Yamashita Masakatsu 愛媛大学, 医学系研究科, 教授 (00311605)
• Co-Investigator(Renkei-kenkyūsha): KUWAHARA Makoto 愛媛大学, 大学院医学系研究科, 助教 (00568214) ; SUZUKI Junpei 愛媛大学, 大学院医学系研究科, 助教(特定教員)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: グルタミン代謝 / ヘルパーT細胞 / エピゲノム / サイトカイン / Th2 / 免疫 / アレルギー・ぜんそく / 炎症

Outline of Final Research Achievements

After receiving antigenic stimulation, the reprogram of metabolic pathway is induced in CD4 T cells and supports rapid clonal expansion. However, the role of metabolic reprograming in the differentiation of helper T cell (Th) subset remains to be elucidated. In this study, we focused on the role of glutamine metabolism in activated CD4 T cells. We found that glutamine metabolism controls chromatin status at the cytokine gene loci and regulates Th differentiation in part via supplementation of apha-ketoglutarate.

Research Products

• [Journal Article] Bach2-Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop. (2016)
  • Author(s): Kuwahara M, Ise W, Ochi M, Suzuki J, Kometani K, Maruyama S, Izumoto M, Matsumoto A, Takemori N, Takemori A, Shinoda K, Nakayama T, Ohara O, Yasukawa M, Sawasaki T, Kurosaki T, Yamashita M.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 12596-12596
  • DOI: 10.1038/ncomms12596
  • Peer Reviewed / Open Access
• [Journal Article] Menin Plays a Critical Role in the Regulation of the Antigen-Specific CD8+ T Cell Response upon Listeria Infection (2016)
  • Author(s): Yamada T, Kanoh M, Nabe S, Yasuoka T, Suzuki J, Matsumoto A, Kuwahara M, Maruyama S, Fujimoto T, Sakisuka R, Yasukawa M, and Yamashita M.
  • Journal Title: Journal of Immunology Volume: 197 Issue: 10 Pages: 4079-4089
  • DOI: 10.4049/jimmunol.1502295
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] TCR-mediated activation of glutamine metabolism plays a critical role in regulating Th2 cell differentiation. (2016)
  • Author(s): Kuwahara M., Inoue K., Imai Y., Yamashita M.
  • Organizer: 第65回日本アレルギー学会学術大会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2016-06-17
• [Presentation] Bach2 controls the thpe-2 immune response by regulating glutamine metabolism (2015)
  • Author(s): KUWAHARA Makoto, OCHI Mizuki, IZUMOTO Maya, KUROSAKI Tomohiro, YAMASHITA Masakatsu
  • Organizer: 第44回日本免疫学会総会・学術集
  • Place of Presentation: 札幌コンベンションセンター (北海道札幌市)
  • Year and Date: 2015-11-18
• [Presentation] A tumor suppressor Menin controls CD8 T cell senescence by regulating energy metabolism (2015)
  • Author(s): SUZUKI Junpei, KUWAHARA Makoto, MARUYAMA Saho, YAMADA Takeshi, YASUOKA Toshiaki, YASUKAWA Masaki, YAMASHITA Masakatsu
  • Organizer: 第44回日本免疫学会総会・学術集
  • Place of Presentation: 札幌コンベンションセンター (北海道札幌市)
  • Year and Date: 2015-11-18
• [Presentation] Menin plays an critical role in the survival of antigen-specific activated CD8+ T cells (2015)
  • Author(s): YAMADA Takeshi, KANOH Makoto, MATSUMOTO Akira, YASUOKA Toshiaki, SUZUKI Junpei, MARUYAMA Saho, KUWAHARA Makoto, YASUKAWA Masaki, YAMASHITA Masakatsu
  • Organizer: 第44回日本免疫学会総会・学術集
  • Place of Presentation: 札幌コンベンションセンター (北海道札幌市)
  • Year and Date: 2015-11-18
• [Presentation] 腫瘍抑制因子Meninは代謝調節を介してCD8 T細胞老化を制御する (2015)
  • Author(s): 鈴木淳平、桑原誠、山田武司、安川正貴、山下政克
  • Organizer: 第３回がんと代謝研究会
  • Place of Presentation: 石川県立音楽堂 (石川県金沢市)
  • Year and Date: 2015-07-16
• [Presentation] Th2細胞分化には細胞内グルタミン代謝が必要である (2015)
  • Author(s): 塩入幹汰、桑原誠、山下政克
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪 (東京都港区)
  • Year and Date: 2015-05-26
• [Remarks] 愛媛大学大学院医学系研究科免疫学・感染防御学ホームページ
  • URL: http://ehime-u-immunology.com/index.html
• [Remarks] 愛媛大学大学院医学系研究科免疫学ホームページ
  • URL: http://ehime-u-immunology.com/