title: Regulator of fatty acid metabolism, acetyl coenzyme a carboxylase 1, controls T cell immunity.
abstract: Fatty acids (FAs) are essential constituents of cell membranes, signaling molecules, and bioenergetic substrates. Because CD8(+) T cells undergo both functional and metabolic changes during activation and differentiation, dynamic changes in FA metabolism also occur. However, the contributions of de novo lipogenesis to acquisition and maintenance of CD8(+) T cell function are unclear. In this article, we demonstrate the role of FA synthesis in CD8(+) T cell immunity. T cell-specific deletion of acetyl coenzyme A carboxylase 1 (ACC1), an enzyme that catalyzes conversion of acetyl coenzyme A to malonyl coenzyme A, a carbon donor for long-chain FA synthesis, resulted in impaired peripheral persistence and homeostatic proliferation of CD8(+) T cells in naive mice. Loss of ACC1 did not compromise effector CD8(+) T cell differentiation upon listeria infection but did result in a severe defect in Ag-specific CD8(+) T cell accumulation because of increased death of proliferating cells. Furthermore, in vitro mitogenic stimulation demonstrated that defective blasting and survival of ACC1-deficient CD8(+) T cells could be rescued by provision of exogenous FA. These results suggest an essential role for ACC1-mediated de novo lipogenesis as a regulator of CD8(+) T cell expansion, and may provide insights for therapeutic targets for interventions in autoimmune diseases, cancer, and chronic infections.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: JangEun
authors.initials: J
authors.lastname: Lee
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Walsh
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Hoehn
authors.forename: David E
authors.initials: DE
authors.lastname: James
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: Yongwon
authors.initials: Y
authors.lastname: Choi
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005227:Fatty Acids / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D050155:Lipogenesis / Q000235:genetics / Q000276:immunology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology / Q000502:physiology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005227:Fatty Acids; D010047:Ovalbumin; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D000103:Acetyl-CoA Carboxylase