Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis

نویسندگان

  • Chih-Hao Chang
  • Jonathan D. Curtis
  • Leonard B. Maggi
  • Brandon Faubert
  • Alejandro V. Villarino
  • David O’Sullivan
  • Stanley Ching-Cheng Huang
  • Gerritje J.W. van der Windt
  • Julianna Blagih
  • Jing Qiu
  • Jason D. Weber
  • Edward J. Pearce
  • Russell G. Jones
  • Erika L. Pearce
چکیده

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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عنوان ژورنال:
  • Cell

دوره 153  شماره 

صفحات  -

تاریخ انتشار 2013