التفاصيل البيبلوغرافية
| العنوان: |
Pyruvate dehydrogenase fuels a critical citrate pool that is essential for Th17 cell effector functions. |
| المؤلفون: |
Soriano-Baguet, Leticia, Grusdat, Melanie, Kurniawan, Henry, Benzarti, Mohaned, Binsfeld, Carole, Ewen, Anouk, Longworth, Joseph, Bonetti, Lynn, Guerra, Luana, Franchina, Davide G., Kobayashi, Takumi, Horkova, Veronika, Verschueren, Charlène, Helgueta, Sergio, Gérard, Deborah, More, Tushar H., Henne, Antonia, Dostert, Catherine, Farinelle, Sophie, Lesur, Antoine |
| المصدر: |
Cell Reports; Mar2023, Vol. 42 Issue 3, pN.PAG-N.PAG, 1p |
| مستخلص: |
Pyruvate dehydrogenase (PDH) is the central enzyme connecting glycolysis and the tricarboxylic acid (TCA) cycle. The importance of PDH function in T helper 17 (Th17) cells still remains to be studied. Here, we show that PDH is essential for the generation of a glucose-derived citrate pool needed for Th17 cell proliferation, survival, and effector function. In vivo , mice harboring a T cell-specific deletion of PDH are less susceptible to developing experimental autoimmune encephalomyelitis. Mechanistically, the absence of PDH in Th17 cells increases glutaminolysis, glycolysis, and lipid uptake in a mammalian target of rapamycin (mTOR)-dependent manner. However, cellular citrate remains critically low in mutant Th17 cells, which interferes with oxidative phosphorylation (OXPHOS), lipid synthesis, and histone acetylation, crucial for transcription of Th17 signature genes. Increasing cellular citrate in PDH-deficient Th17 cells restores their metabolism and function, identifying a metabolic feedback loop within the central carbon metabolism that may offer possibilities for therapeutically targeting Th17 cell-driven autoimmunity. [Display omitted] • PDH-ablation in T cells lowers Th17 cell-mediated autoimmunity • PDH is essential for the pathogenic function of Th17 cells and IL-17 production • PDH fuels a citrate pool controlling glycolysis, glutaminolysis, and lipids • PDH controls histone acetylation and Th17 cell gene transcription Pyruvate dehydrogenase (PDH) connects glycolysis with the mitochondrial tricarboxylic acid (TCA) cycle. Soriano-Baguet et al. show that PDH directs a glucose-derived citrate pool that coordinates the central carbon metabolism and histone acetylation and is essential for Th17 cell function. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
