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ホスホエノールピルビン酸はJunBに依存するTh17の転写プログラムを制御する
https://doi.org/10.15102/1394.00002640
https://doi.org/10.15102/1394.00002640c730455c-da5e-4e74-96ca-6b4855e13e6f
名前 / ファイル | ライセンス | アクション |
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Tsung-YenHuangExamAbstract (49.1 kB)
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Tsung-YenHuang_Full_Text (5.5 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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公開日 | 2023-05-09 | |||||||
タイトル | ||||||||
言語 | ja | |||||||
タイトル | ホスホエノールピルビン酸はJunBに依存するTh17の転写プログラムを制御する | |||||||
タイトル | ||||||||
言語 | en | |||||||
タイトル | Phosphoenolpyruvate Regulates the JunB-Dependent Pathogenic Th17 Transcriptional Program | |||||||
言語 | ||||||||
言語 | eng | |||||||
資源タイプ | ||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
資源タイプ | doctoral thesis | |||||||
ID登録 | ||||||||
ID登録 | 10.15102/1394.00002640 | |||||||
ID登録タイプ | JaLC | |||||||
アクセス権 | ||||||||
アクセス権 | open access | |||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
著者 (英) |
Huang, Tsung-Yen
× Huang, Tsung-Yen
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抄録 | ||||||||
内容記述タイプ | Other | |||||||
内容記述 | Aerobic glycolysis, a metabolic pathway essential for effector T cell survival and proliferation, regulates the differentiation of autoimmune T helper (Th)17 cells, but the mechanism underlying this regulation is largely unknown. Here, we identify a glycolytic intermediate metabolite, phosphoenolpyruvate (PEP), as a negative regulator of Th17 differentiation. PEP supplementation or inhibition of downstream glycolytic enzymes in differentiating Th17 cells increases intracellular PEP levels and inhibits the expression of Th17 signature molecules, such as IL-17A. However, PEP supplementation does not significantly affect metabolic reprogramming, cell proliferation, and survival of differentiating Th17 cells. Mechanistically, PEP regulates the JunB-dependent pathogenic Th17 transcriptional program by inhibiting the DNA-binding activity of the JunB/BATF/IRF4 complex. Furthermore, daily administration of PEP to mice inhibits the generation of Th17 cells and ameliorates Th17-dependent autoimmune encephalomyelitis. These data demonstrate that PEP links aerobic glycolysis to the JunB-dependent pathogenic Th17 transcriptional program, suggesting the therapeutic potential of PEP for autoimmune diseases. | |||||||
言語 | en | |||||||
口頭試問日 | ||||||||
2023-01-23 | ||||||||
学位授与年月日 | ||||||||
学位授与年月日 | 2023-03-31 | |||||||
学位名 | ||||||||
学位名 | Doctor of Philosophy | |||||||
学位授与番号 | ||||||||
学位授与番号 | 甲第120号 | |||||||
学位授与機関 | ||||||||
学位授与機関識別子Scheme | kakenhi | |||||||
学位授与機関識別子 | 38005 | |||||||
学位授与機関名 | Okinawa Institute of Science and Technology Graduate University | |||||||
著者版フラグ | ||||||||
出版タイプ | VoR | |||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
権利 | ||||||||
権利情報 | © 2023 The Author. |