title: Posttranscriptional control of T cell effector function by aerobic glycolysis.
abstract: 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.
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Chang
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Curtis
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Maggi
authors.forename: Brandon
authors.initials: B
authors.lastname: Faubert
authors.forename: Alejandro V
authors.initials: AV
authors.lastname: Villarino
authors.forename: David
authors.initials: D
authors.lastname: O'Sullivan
authors.forename: Stanley Ching-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: Gerritje J W
authors.initials: GJ
authors.lastname: van der Windt
authors.forename: Julianna
authors.initials: J
authors.lastname: Blagih
authors.forename: Jing
authors.initials: J
authors.lastname: Qiu
authors.forename: Jason D
authors.initials: JD
authors.lastname: Weber
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Pearce
authors.forename: Russell G
authors.initials: RG
authors.lastname: Jones
authors.forename: Erika L
authors.initials: EL
authors.lastname: Pearce
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D049109:Cell Proliferation; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006019:Glycolysis; D007371:Interferon-gamma / Q000235:genetics; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010085:Oxidative Phosphorylation; D014176:Protein Biosynthesis; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D007371:Interferon-gamma; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases