{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:38:12Z","timestamp":1791221892187,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013specific 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1302985","type":"journal-article","created":{"date-parts":[[2014,2,25]],"date-time":"2014-02-25T01:13:11Z","timestamp":1393290791000},"page":"3190-3199","source":"Crossref","is-referenced-by-count":194,"title":["Regulator of Fatty Acid Metabolism, Acetyl Coenzyme A Carboxylase 1, Controls T Cell Immunity"],"prefix":"10.1093","volume":"192","author":[{"given":"JangEun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle L","family":"Hoehn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Virginia Health System , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E","family":"James","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research , Darlinghurst, New South Wales 2010,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E John","family":"Wherry","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongwon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,4,1]]},"reference":[{"key":"2025032404215840700_r1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/ni912","article-title":"Dynamic programming of CD8+ T lymphocyte responses","volume":"4","author":"van Stipdonk","year":"2003","journal-title":"Nat. Immunol."},{"key":"2025032404215840700_r2","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.bbalip.2012.09.003","article-title":"Yeast and cancer cells - common principles in lipid metabolism","volume":"1831","author":"Natter","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"2025032404215840700_r3","doi-asserted-by":"crossref","first-page":"25847","DOI":"10.1074\/jbc.R200008200","article-title":"The Ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind","volume":"277","author":"Hannun","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2025032404215840700_r4","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1194\/jlr.M037044","article-title":"Fatty acid remodeling in cellular glycerophospholipids following the activation of human T cells","volume":"54","author":"Robichaud","year":"2013","journal-title":"J. Lipid Res."},{"key":"2025032404215840700_r5","doi-asserted-by":"crossref","first-page":"7009","DOI":"10.4049\/jimmunol.166.12.7009","article-title":"Cutting edge: lipid raft integrity affects the efficiency of MHC class I tetramer binding and cell surface TCR arrangement on CD8+ T cells","volume":"166","author":"Drake","year":"2001","journal-title":"J. Immunol."},{"key":"2025032404215840700_r6","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev-nutr-071811-150726","article-title":"Resolvins: anti-inflammatory and proresolving mediators derived from omega-3 polyunsaturated fatty acids","volume":"32","author":"Zhang","year":"2012","journal-title":"Annu. Rev. Nutr."},{"key":"2025032404215840700_r7","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.immuni.2013.05.015","article-title":"Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation","volume":"38","author":"Yan","year":"2013","journal-title":"Immunity"},{"key":"2025032404215840700_r8","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1146\/annurev-immunol-031210-101405","article-title":"The inflammasome NLRs in immunity, inflammation, and associated diseases","volume":"29","author":"Davis","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"2025032404215840700_r9","doi-asserted-by":"crossref","first-page":"11276","DOI":"10.1073\/pnas.0601280103","article-title":"Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis","volume":"103","author":"Hudert","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404215840700_r10","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1093\/jn\/133.6.1913","article-title":"Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts","volume":"133","author":"Fan","year":"2003","journal-title":"J. Nutr."},{"key":"2025032404215840700_r11","doi-asserted-by":"crossref","first-page":"6236","DOI":"10.4049\/jimmunol.181.9.6236","article-title":"n-3 polyunsaturated fatty acids suppress the localization and activation of signaling proteins at the immunological synapse in murine CD4+ T cells by affecting lipid raft formation","volume":"181","author":"Kim","year":"2008","journal-title":"J. Immunol."},{"key":"2025032404215840700_r12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nature08097","article-title":"Enhancing CD8 T-cell memory by modulating fatty acid metabolism","volume":"460","author":"Pearce","year":"2009","journal-title":"Nature"},{"key":"2025032404215840700_r13","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1073\/pnas.97.4.1444","article-title":"The subcellular localization of acetyl-CoA carboxylase 2","volume":"97","author":"Abu-Elheiga","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404215840700_r14","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1007\/s11745-004-1329-9","article-title":"Structure and function of animal fatty acid synthase","volume":"39","author":"Chirala","year":"2004","journal-title":"Lipids"},{"key":"2025032404215840700_r15","doi-asserted-by":"crossref","first-page":"11466","DOI":"10.1073\/pnas.93.21.11466","article-title":"Cloning of human acetyl-CoA carboxylase-beta and its unique features","volume":"93","author":"Ha","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404215840700_r16","doi-asserted-by":"crossref","first-page":"10669","DOI":"10.1074\/jbc.272.16.10669","article-title":"Human acetyl-CoA carboxylase 2. Molecular cloning, characterization, chromosomal mapping, and evidence for two isoforms","volume":"272","author":"Abu-Elheiga","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2025032404215840700_r17","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1146\/annurev.bi.52.070183.002541","article-title":"Fatty acid synthesis and its regulation","volume":"52","author":"Wakil","year":"1983","journal-title":"Annu. Rev. Biochem."},{"key":"2025032404215840700_r18","doi-asserted-by":"crossref","first-page":"S138","DOI":"10.1194\/jlr.R800079-JLR200","article-title":"Fatty acid metabolism: target for metabolic syndrome","volume":"50","author":"Wakil","year":"2009","journal-title":"J. Lipid Res."},{"key":"2025032404215840700_r19","doi-asserted-by":"crossref","first-page":"8552","DOI":"10.1073\/pnas.0603115103","article-title":"Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis","volume":"103","author":"Mao","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404215840700_r20","doi-asserted-by":"crossref","first-page":"17576","DOI":"10.1073\/pnas.0909055106","article-title":"aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues","volume":"106","author":"Mao","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404215840700_r21","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S0899-9007(99)00266-X","article-title":"Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology","volume":"16","author":"Kuhajda","year":"2000","journal-title":"Nutrition"},{"key":"2025032404215840700_r22","doi-asserted-by":"crossref","first-page":"6379","DOI":"10.1073\/pnas.91.14.6379","article-title":"Fatty acid synthesis: a potential selective target for antineoplastic therapy","volume":"91","author":"Kuhajda","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404215840700_r23","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S1535-6108(04)00055-8","article-title":"The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer","volume":"5","author":"Graner","year":"2004","journal-title":"Cancer Cell"},{"key":"2025032404215840700_r24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/sj.onc.1208174","article-title":"Fatty acid synthase inhibitors are chemopreventive for mammary cancer in neu-N transgenic mice","volume":"24","author":"Alli","year":"2005","journal-title":"Oncogene"},{"key":"2025032404215840700_r25","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/ijc.20754","article-title":"Pharmacological and small interference RNA-mediated inhibition of breast cancer-associated fatty acid synthase (oncogenic antigen-519) synergistically enhances Taxol (paclitaxel)-induced cytotoxicity","volume":"115","author":"Menendez","year":"2005","journal-title":"Int. J. Cancer"},{"key":"2025032404215840700_r26","doi-asserted-by":"crossref","first-page":"6201","DOI":"10.4049\/jimmunol.181.9.6201","article-title":"Mycobacterium bovis bacille Calmette-Gu\u00e9rin infection in the CNS suppresses experimental autoimmune encephalomyelitis and Th17 responses in an IFN-gamma-independent manner","volume":"181","author":"Lee","year":"2008","journal-title":"J. Immunol."},{"key":"2025032404215840700_r27","first-page":"E372","article-title":"Measurement of fractional lipid synthesis using deuterated water (2H2O) and mass isotopomer analysis","volume":"266","author":"Lee","year":"1994","journal-title":"Am. J. Physiol."},{"key":"2025032404215840700_r28","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.4049\/jimmunol.179.4.2074","article-title":"Generation of CD8 T cell memory is regulated by IL-12","volume":"179","author":"Pearce","year":"2007","journal-title":"J. Immunol."},{"key":"2025032404215840700_r29","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/ni.2570","article-title":"Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity","volume":"14","author":"Kidani","year":"2013","journal-title":"Nat. Immunol."},{"key":"2025032404215840700_r30","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0005-2760(90)90076-A","article-title":"Fatty acid metabolism in human lymphocytes. I. Time-course changes in fatty acid composition and membrane fluidity during blastic transformation of peripheral blood lymphocytes","volume":"1044","author":"Anel","year":"1990","journal-title":"Biochim. Biophys. Acta"},{"key":"2025032404215840700_r31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1432-1033.1981.tb05230.x","article-title":"Activation of lymphocyte populations with concanavalin A or with lipoprotein and lipopeptide from the outer cell wall of Escherichia coli: correlation of early membrane changes with induction of macromolecular synthesis","volume":"115","author":"Resch","year":"1981","journal-title":"Eur. J. Biochem."},{"key":"2025032404215840700_r32","doi-asserted-by":"crossref","first-page":"12011","DOI":"10.1073\/pnas.0505714102","article-title":"Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal","volume":"102","author":"Abu-Elheiga","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404215840700_r33","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/ni1268","article-title":"Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin","volume":"6","author":"Intlekofer","year":"2005","journal-title":"Nat. Immunol."},{"key":"2025032404215840700_r34","doi-asserted-by":"crossref","first-page":"e33823","DOI":"10.1371\/journal.pone.0033823","article-title":"SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids","volume":"7","author":"Mason","year":"2012","journal-title":"PLoS ONE"},{"key":"2025032404215840700_r35","doi-asserted-by":"crossref","first-page":"5287","DOI":"10.1158\/0008-5472.CAN-05-1489","article-title":"Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival","volume":"66","author":"Chaj\u00e8s","year":"2006","journal-title":"Cancer Res."},{"key":"2025032404215840700_r36","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.immuni.2008.11.002","article-title":"Homeostasis of naive and memory T cells","volume":"29","author":"Surh","year":"2008","journal-title":"Immunity"},{"key":"2025032404215840700_r37","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1084\/jem.179.4.1127","article-title":"Turnover of naive- and memory-phenotype T cells","volume":"179","author":"Tough","year":"1994","journal-title":"J. Exp. Med."},{"key":"2025032404215840700_r38","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.biochi.2004.09.018","article-title":"SREBP transcription factors: master regulators of lipid homeostasis","volume":"86","author":"Eberl\u00e9","year":"2004","journal-title":"Biochimie"},{"key":"2025032404215840700_r39","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.cmet.2008.07.007","article-title":"SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth","volume":"8","author":"Porstmann","year":"2008","journal-title":"Cell Metab."},{"key":"2025032404215840700_r40","doi-asserted-by":"crossref","first-page":"11245","DOI":"10.1073\/pnas.0404297101","article-title":"Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver","volume":"101","author":"Chen","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404215840700_r41","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/S0006-291X(03)00265-1","article-title":"Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains","volume":"302","author":"Swinnen","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2025032404215840700_r42","doi-asserted-by":"crossref","first-page":"37901","DOI":"10.1074\/jbc.M504282200","article-title":"Local change in phospholipid composition at the cleavage furrow is essential for completion of cytokinesis","volume":"280","author":"Emoto","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2025032404215840700_r43","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.cell.2013.05.016","article-title":"Posttranscriptional control of T cell effector function by aerobic glycolysis","volume":"153","author":"Chang","year":"2013","journal-title":"Cell"},{"key":"2025032404215840700_r44","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1182\/blood-2007-06-096297","article-title":"IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival","volume":"111","author":"Wofford","year":"2008","journal-title":"Blood"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/7\/3190\/61760087\/1302985.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/7\/3190\/61760087\/1302985.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T03:52:07Z","timestamp":1742788327000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/192\/7\/3190\/8001567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,1]]},"references-count":44,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1302985","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,4]]},"published":{"date-parts":[[2014,4,1]]}}}