دورية أكاديمية
Pyruvate dehydrogenase fuels a critical citrate pool that is essential for Th17 cell effector functions
| العنوان: | Pyruvate dehydrogenase fuels a critical citrate pool that is essential for Th17 cell effector functions |
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| 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, Gérardy, Jean Jacques, Jäger, Christian, Mittelbronn, Michel, Sinkkonen, Lasse, Hiller, Karsten, Meiser, Johannes, Brenner, Dirk |
| المصدر: | Soriano-Baguet , L , Grusdat , M , Kurniawan , H , Benzarti , M , Binsfeld , C , Ewen , A , Longworth , J , Bonetti , L , Guerra , L , Franchina , D G , Kobayashi , T , Horkova , V , Verschueren , C , Helgueta , S , Gérard , D , More , T H , Henne , A , Dostert , C , Farinelle , S , Lesur , A , Gérardy , J J , Jäger , C , Mittelbronn , M , Sinkkonen , L , .... |
| سنة النشر: | 2023 |
| المجموعة: | University of Southern Denmark: Research Output / Syddansk Universitet |
| مصطلحات موضوعية: | acetyl-CoA, citrate, CP: Immunology, CP: Metabolism, epigenetics, experimental autoimmune encephalomyelitis, glucose metabolism, histone acetylation, IL-17, pyruvate dehydrogenase, T cells, Th17 cells |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://portal.findresearcher.sdu.dk/da/publications/49178a4a-6d9e-4128-ac35-fff19082546cTest |
| DOI: | 10.1016/j.celrep.2023.112153 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2023.112153Test https://portal.findresearcher.sdu.dk/da/publications/49178a4a-6d9e-4128-ac35-fff19082546cTest https://findresearcher.sdu.dk/ws/files/223017088/1_s2.0_S221112472300164X_main.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.4B112D7F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.celrep.2023.112153 |
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