Investigations of the role of glutamine metabolism in the T cell fate determination
| Project/Area Number |
16K19158
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Ehime University |
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Principal Investigator |
Kuwahara Makoto 愛媛大学, 医学部附属病院, 助教(病院教員) (00568214)
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| Research Collaborator |
YAMASHITA Masakatsu
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | T細胞運命決定 / グルタミン代謝 / Th2 / Utx / T 細胞老化 / a-ケトグルタル酸 / H3K27me2/3 / 活性化 T 細胞運命決定 / 獲得免疫 |
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| Outline of Final Research Achievements |
We assessed the role of glutamine metabolism in the fate determination of activated T cells in this study. The deprivation of glutamine from culture medium or the pharmacological inhibition of glutamine metabolism suppressed Th2 differentiation and the induction of T cell senescent phenotype in vitro. The administration of alpha-ketoglutarate (α-KG) in cultures under glutamine-deprived conditions restored Th2 differentiation and induced T cell senescent phenotype indicating thatα-KG derived from glutamine is required for Th2 differentiation and induction of T cell senescent phenotype. Furthermore, we found that α-KG-dependent demethylation of the Th2 cytokine gene loci by the H3K27 demethylase Utx is required for the efficient Th2 differentiation. Alpha-KG-dependent histone H3K27 demethylation is also involved in the induction of senescence. These findings reveal the novel role of glutamine metabolism in regulating Th2 differentiation and induction of T cell senescent phenotype.
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] Inflammatory responses induce an identity crisis of alveolar macrophages, leading to pulmonary alveolar proteinosis.2017
Author(s)
Ebina-Shibuya R, Matsumoto M, Kuwahara M, Jang KJ, Sugai M, Ito Y, Funayama R, Nakayama K, Sato Y, Ishii N, Okamura Y, Kinoshita K, Kometani K, Kurosaki T, Muto A, Ichinose M, Yamashita M, Igarashi K.
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Journal Title
The Journal of biological chemistry
Volume: 292
Issue: 44
Pages: 18098-18112
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Nature Communications
Volume: 7
Issue: 1
Pages: 12596-12596
DOI
Related Report
Peer Reviewed / Open Access
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