Cell
Volume 153, Issue 6, 6 June 2013, Pages 1239-1251
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Article
Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis

https://doi.org/10.1016/j.cell.2013.05.016Get rights and content
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Highlights

  • T cells do not require aerobic glycolysis to fuel proliferation or survival

  • Glycolysis is specifically required for effector cytokine production in T cells

  • When not engaged in glycolysis, GAPDH binds to cytokine mRNA

  • Changes in available GAPDH regulate cytokine mRNA translation

Summary

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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