title: The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function.
abstract: CD4 T cell activation leads to proliferation and differentiation into effector (Teff) or regulatory (Treg) cells that mediate or control immunity. While each subset prefers distinct glycolytic or oxidative metabolic programs in vitro, requirements and mechanisms that control T cell glucose uptake and metabolism in vivo are uncertain. Despite expression of multiple glucose transporters, Glut1 deficiency selectively impaired metabolism and function of thymocytes and Teff. Resting T cells were normal until activated, when Glut1 deficiency prevented increased glucose uptake and glycolysis, growth, proliferation, and decreased Teff survival and differentiation. Importantly, Glut1 deficiency decreased Teff expansion and the ability to induce inflammatory disease in vivo. Treg cells, in contrast, were enriched in vivo and appeared functionally unaffected and able to suppress Teff, irrespective of Glut1 expression. These data show a selective in vivo requirement for Glut1 in metabolic reprogramming of CD4 T cell activation and Teff expansion and survival.
authors.affiliation: Department of Pharmacology and Cancer Biology, Immunology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Macintyre
authors.affiliation: Department of Pharmacology and Cancer Biology, Immunology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Gerriets
authors.affiliation: Department of Pharmacology and Cancer Biology, Immunology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA.
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Nichols
authors.affiliation: Department of Pharmacology and Cancer Biology, Immunology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Michalek
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Rudolph
authors.affiliation: Division of Hematological Malignancies and Cellular Therapy, Department of Medicine, Duke University, Durham, NC 27710, USA.
authors.forename: Divino
authors.initials: D
authors.lastname: Deoliveira
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Anderson
authors.affiliation: Fraternal Order of Eagles Diabetes Research Center, Division of Endocrinology and Metabolism, Department of Medicine, Carver College of Medicine University of Iowa, Iowa City, IA 52242, USA.
authors.forename: E Dale
authors.initials: ED
authors.lastname: Abel
authors.affiliation: Division of Hematological Malignancies and Cellular Therapy, Department of Medicine, Duke University, Durham, NC 27710, USA.
authors.forename: Benny J
authors.initials: BJ
authors.lastname: Chen
authors.affiliation: Department of Pathology, Duke University, Durham, NC 27710, USA.
authors.forename: Laura P
authors.initials: LP
authors.lastname: Hale
authors.affiliation: Department of Pharmacology and Cancer Biology, Immunology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Rathmell
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002470:Cell Survival; D003092:Colitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D018398:Homeodomain Proteins; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; C495689:Slc2a3 protein, mouse; C064658:RAG-1 protein; D005947:Glucose