TY - JOUR
T1 - XPosttranscriptional control of T cell effector function by aerobic glycolysis
AU - Chang, Chih Hao
AU - Curtis, Jonathan D.
AU - Maggi, Leonard B.
AU - Faubert, Brandon
AU - Villarino, Alejandro V.
AU - O'Sullivan, David
AU - Huang, Stanley Ching Cheng
AU - Van Der Windt, Gerritje J.W.
AU - Blagih, Julianna
AU - Qiu, Jing
AU - Weber, Jason D.
AU - Pearce, Edward J.
AU - Jones, Russell G.
AU - Pearce, Erika L.
N1 - Funding Information:
We thank Andrey Shaw, Ken Murphy, Skip Virgin, Abul Abbas, Eyal Amiel, Rong Zeng, Qiongyu Chen, Monika Vig, Georgia Perona-Wright, Bart Everts, and the Goodman Cancer Research Centre Metabolomics Core Facility at McGIll University. This work was supported in part by grants from the NIH (AI091965 and CA158823 to E.L.P. and CA164062 to E.J.P.), CIHR (MOP-93799 to R.G.J.), The Arthritis Society of Canada (R.G.J.), NWO (G.J.W.v.d.W.), and the Emerald Foundation Young Investigator Award (E.L.P.). C.-H.C., L.B.M., J.D.W., A.V.V., E.J.P., R.G.J., and E.L.P. designed the research. C.C., J.D.C., S.C.-C.H., G.J.W.v.d.W, D.O., J.B., B.F., J.Q., and E.L.P. analyzed data. C.C., J.D.C., L.B.M., B.F., S.C.-C.H., D.O., G.J.W.v.d.W., J.Q., and E.L.P. performed experiments. C.C., E.J.P., and E.L.P. contributed to the preparation of the manuscript. C.C. and E.L.P. wrote the manuscript.
PY - 2013/6/6
Y1 - 2013/6/6
N2 - 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. PaperFlick
AB - 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. PaperFlick
UR - https://www.scopus.com/pages/publications/84878831880
U2 - 10.1016/j.cell.2013.05.016
DO - 10.1016/j.cell.2013.05.016
M3 - Article
C2 - 23746840
AN - SCOPUS:84878831880
SN - 0092-8674
VL - 153
SP - 1239
JO - Cell
JF - Cell
IS - 6
ER -