Posttranscriptional control of T cell effector function by aerobic glycolysis.
Posttranscriptional control of T cell effector function by aerobic glycolysis.
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DOI：
10.1016/j.cell.2013.05.016
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发表时间：
2013-06-06
期刊：
影响因子：
64.5
通讯作者：
Pearce EL
中科院分区：
文献类型：
--
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
从氧化磷酸化（OXPHOS）到有氧糖酵解的“转换”是T细胞活化的标志，并且被认为是满足增殖的代谢需求所需的。然而，为什么增殖细胞采用这种效率较低的代谢，特别是在充满氧气的环境中，仍然不完全清楚。我们在这里表明，有氧糖酵解是T细胞中效应子功能所必需的，但这一途径对增殖或存活不是必需的。当活化的T细胞被提供共刺激和生长因子，但被阻止参与糖酵解时，它们产生IFN-γ的能力明显受损。这种缺陷是翻译性的，并通过糖酵解酶GAPDH与IFN-γ mRNA 3′ UTR内富含AU的元件的结合来调节。GAPDH通过参与/脱离糖酵解并通过其表达的波动来控制效应细胞因子的产生。因此，有氧糖酵解是控制细胞功能所需的代谢调节信号机制。
A “switch” from oxidative phosphorylation (OXPHOS) to aerobic glycolysis is a hallmark of T cell activation and is thought to be required to meet the metabolic demands of proliferation. However, why proliferating cells adopt this less efficient metabolism, especially in an oxygen-replete environment, remains incompletely understood. We show here that aerobic glycolysis is specifically required for effector function in T cells but that this pathway is not necessary for proliferation or survival. When activated T cells are provided with costimulation and growth factors but are blocked from engaging glycolysis, their ability to produce IFN-γ is markedly compromised. This defect is translational and is regulated by the binding of the glycolysis enzyme GAPDH to AU-rich elements within the 3′ UTR of IFN-γ mRNA. GAPDH, by engaging/disengaging glycolysis and through fluctuations in its expression, controls effector cytokine production. Thus, aerobic glycolysis is a metabolically regulated signaling mechanism needed to control cellular function.
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