{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:35:41Z","timestamp":1793424941119,"version":"4.5.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"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":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Access to nutrients is critical for an effective T cell immune response to infection. Although transporters for sugars and amino acids have previously been described in the context of the CD8+ T cell immune response, the active transport of exogenous fatty acids has remained enigmatic. In this study, we discovered that the sodium-dependent lysophosphatidylcholine (LPC) transporter major facilitator superfamily domain containing 2A (MFSD2A) is upregulated on activated CD8+ T cells and is required for memory T cell maintenance. MFSD2A deficiency in mice resulted in decreased import of LPC esterified to long chain fatty acids into activated CD8+ T cells, and MFSD2A-deficient cells are at a competitive disadvantage resulting in reduced memory T cell formation and maintenance and reduced response to secondary infection. Mechanistically, import of LPCs was required to maintain T cell homeostatic turnover, which when lost resulted in a decreased memory T cell pool and thus a reduced secondary response to repeat infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1801585","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T20:14:06Z","timestamp":1558728846000},"page":"117-126","source":"Crossref","is-referenced-by-count":37,"title":["The Lysophosphatidylcholine Transporter MFSD2A Is Essential for CD8+ Memory T Cell Maintenance and Secondary Response to Infection"],"prefix":"10.1093","volume":"203","author":[{"given":"Ann R","family":"Piccirillo","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4141-3050","authenticated-orcid":false,"given":"Eric J","family":"Hyzny","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6918-1159","authenticated-orcid":false,"given":"Lisa Y","family":"Beppu","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley V","family":"Menk","sequence":"additional","affiliation":[{"name":"Tumor Microenvironment Center, UPMC Hillman Cancer Center , Pittsburgh, PA 15232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callen T","family":"Wallace","sequence":"additional","affiliation":[{"name":"Center for Biologic Imaging, University of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8371-3345","authenticated-orcid":false,"given":"William F","family":"Hawse","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0955-200X","authenticated-orcid":false,"given":"Heather M","family":"Buechel","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8981-1376","authenticated-orcid":false,"given":"Bernice H","family":"Wong","sequence":"additional","affiliation":[{"name":"Signature Research Program in Cardiovascular and Metabolic Diseases, Duke-National University of Singapore Graduate Medical School , Singapore 159857 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9189-4585","authenticated-orcid":false,"given":"Juat Chin","family":"Foo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National University of Singapore , Singapore 117597 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3050-634X","authenticated-orcid":false,"given":"Amaury","family":"Cazenave-Gassiot","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National University of Singapore , Singapore 117597 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus R","family":"Wenk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National University of Singapore , Singapore 117597 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg M","family":"Delgoffe","sequence":"additional","affiliation":[{"name":"Tumor Microenvironment Center, UPMC Hillman Cancer Center , Pittsburgh, PA 15232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4092-1552","authenticated-orcid":false,"given":"Simon C","family":"Watkins","sequence":"additional","affiliation":[{"name":"Center for Biologic Imaging, University of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Silver","sequence":"additional","affiliation":[{"name":"Signature Research Program in Cardiovascular and Metabolic Diseases, Duke-National University of Singapore Graduate Medical School , Singapore 159857 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0388-430X","authenticated-orcid":false,"given":"Louise M","family":"D\u2019Cruz","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2025030418133395100_r1","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1038\/ni.3031","article-title":"Molecular regulation of effector and memory T cell differentiation","volume":"15","author":"Chang","year":"2014","journal-title":"Nat. Immunol."},{"key":"2025030418133395100_r2","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1084\/jem.20151159","article-title":"T cell metabolism drives immunity","volume":"212","author":"Buck","year":"2015","journal-title":"J. Exp. Med."},{"key":"2025030418133395100_r3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.coi.2015.01.015","article-title":"Sugar, fat, and protein: new insights into what T cells crave","volume":"33","author":"Delgoffe","year":"2015","journal-title":"Curr. Opin. Immunol."},{"key":"2025030418133395100_r4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.immuni.2014.06.005","article-title":"Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development. [Published erratum appears in 2018 Immunity 49: 375\u2013376.]","volume":"41","author":"O\u2019Sullivan","year":"2014","journal-title":"Immunity"},{"key":"2025030418133395100_r5","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.cell.2015.03.021","article-title":"IL-7-Induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity","volume":"161","author":"Cui","year":"2015","journal-title":"Cell"},{"key":"2025030418133395100_r6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cmet.2014.05.004","article-title":"The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function","volume":"20","author":"Macintyre","year":"2014","journal-title":"Cell Metab."},{"key":"2025030418133395100_r7","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/ni.2556","article-title":"Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. [Published erratum appears in 2014 Nat. Immunol. 15: 109.]","volume":"14","author":"Sinclair","year":"2013","journal-title":"Nat. Immunol."},{"key":"2025030418133395100_r8","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":"2025030418133395100_r9","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.it.2014.12.005","article-title":"Fatty acid metabolism in the regulation of T cell function","volume":"36","author":"Lochner","year":"2015","journal-title":"Trends Immunol."},{"key":"2025030418133395100_r10","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.4049\/jimmunol.1003613","article-title":"Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets","volume":"186","author":"Michalek","year":"2011","journal-title":"J. Immunol."},{"key":"2025030418133395100_r11","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":"2025030418133395100_r12","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2011.09.021","article-title":"The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation","volume":"35","author":"Wang","year":"2011","journal-title":"Immunity"},{"key":"2025030418133395100_r13","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/ni.2386","article-title":"Metabolic checkpoints in activated T cells","volume":"13","author":"Wang","year":"2012","journal-title":"Nat. Immunol."},{"key":"2025030418133395100_r14","first-page":"504","article-title":"Etomoxir actions on regulatory and memory T cells are independent of cpt1a-mediated fatty acid oxidation","volume-title":"Cell Metab.","author":"Raud","year":"2018"},{"key":"2025030418133395100_r15","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0050629","article-title":"Major facilitator superfamily domain-containing protein 2a (MFSD2A) has roles in body growth, motor function, and lipid metabolism","volume":"7","author":"Berger","year":"2012","journal-title":"PLoS One"},{"key":"2025030418133395100_r16","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nature13241","article-title":"Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid","volume":"509","author":"Nguyen","year":"2014","journal-title":"Nature"},{"key":"2025030418133395100_r17","doi-asserted-by":"crossref","first-page":"10501","DOI":"10.1074\/jbc.M116.721340","article-title":"Mfsd2a is a transporter for the essential \u03c9-3 fatty acid docosahexaenoic acid (DHA) in eye and is important for photoreceptor cell development","volume":"291","author":"Wong","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2025030418133395100_r18","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/ng.3313","article-title":"A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome","volume":"47","author":"Alakbarzade","year":"2015","journal-title":"Nat. Genet."},{"key":"2025030418133395100_r19","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/ng.3311","article-title":"Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome","volume":"47","author":"Guemez-Gamboa","year":"2015","journal-title":"Nat. Genet."},{"key":"2025030418133395100_r20","first-page":"227","article-title":"Homozygous mutation in MFSD2A, encoding a lysolipid transporter for docosahexanoic acid, is associated with microcephaly and hypomyelination","volume-title":"Neurogenetics","author":"Harel","year":"2018"},{"key":"2025030418133395100_r21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2006443","article-title":"The lysolipid transporter Mfsd2a regulates lipogenesis in the developing brain","volume":"16","author":"Chan","year":"2018","journal-title":"PLoS Biol."},{"key":"2025030418133395100_r22","doi-asserted-by":"crossref","first-page":"7757","DOI":"10.1074\/jbc.270.13.7757","article-title":"Lysophosphatidylcholine and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine inhibit the CDP-choline pathway of phosphatidylcholine synthesis at the CTP:phosphocholine cytidylyltransferase step","volume":"270","author":"Boggs","year":"1995","journal-title":"J. Biol. Chem."},{"key":"2025030418133395100_r23","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1194\/jlr.M500054-JLR200","article-title":"Endothelial lipase releases saturated and unsaturated fatty acids of high density lipoprotein phosphatidylcholine","volume":"46","author":"Gauster","year":"2005","journal-title":"J. Lipid Res."},{"key":"2025030418133395100_r24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.atherosclerosis.2009.05.029","article-title":"Metabolism and atherogenic disease association of lysophosphatidylcholine","volume":"208","author":"Schmitz","year":"2010","journal-title":"Atherosclerosis"},{"key":"2025030418133395100_r25","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/MOL.0b013e3282fee935","article-title":"Role of phosphatidylcholine biosynthesis in the regulation of lipoprotein homeostasis","volume":"19","author":"Vance","year":"2008","journal-title":"Curr. Opin. Lipidol."},{"key":"2025030418133395100_r26","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/nri1710","article-title":"Fuel feeds function: energy metabolism and the T-cell response","volume":"5","author":"Fox","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"2025030418133395100_r27","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"},{"key":"2025030418133395100_r28","doi-asserted-by":"crossref","first-page":"483","DOI":"10.3389\/fimmu.2014.00483","article-title":"Fatty acids, lipid mediators, and T-cell function","volume":"5","author":"de Jong","year":"2014","journal-title":"Front. Immunol."},{"key":"2025030418133395100_r29","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s11239-007-0158-x","article-title":"Lysophosphatidylcholine upregulates LOX-1, chemokine receptors, and activation-related transcription factors in human T-cell line Jurkat","volume":"26","author":"Hara","year":"2008","journal-title":"J. Thromb. Thrombolysis"},{"key":"2025030418133395100_r30","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1161\/01.RES.80.5.638","article-title":"Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T lymphocytes","volume":"80","author":"Nishi","year":"1997","journal-title":"Circ. Res."},{"key":"2025030418133395100_r31","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1161\/01.RES.83.5.508","article-title":"Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes","volume":"83","author":"Nishi","year":"1998","journal-title":"Circ. Res."},{"key":"2025030418133395100_r32","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"2025030418133395100_r33","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.bbamem.2006.09.026","article-title":"Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism","volume":"1768","author":"Meyer zu Heringdorf","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"2025030418133395100_r34","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.bbrc.2004.11.120","article-title":"Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor","volume":"326","author":"Soga","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2025030418133395100_r35","doi-asserted-by":"crossref","first-page":"S311","DOI":"10.1194\/jlr.R800049-JLR200","article-title":"Membrane phospholipid synthesis and endoplasmic reticulum function","volume":"50","author":"Fagone","year":"2009","journal-title":"J. Lipid Res."},{"key":"2025030418133395100_r36","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.immuni.2011.12.007","article-title":"Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development","volume":"36","author":"van der Windt","year":"2012","journal-title":"Immunity"},{"key":"2025030418133395100_r37","doi-asserted-by":"crossref","first-page":"14336","DOI":"10.1073\/pnas.1221740110","article-title":"CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability","volume":"110","author":"van der Windt","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030418133395100_r38","doi-asserted-by":"crossref","first-page":"643","DOI":"10.4049\/jimmunol.1602110","article-title":"Early inhibition of fatty acid synthesis reduces generation of memory precursor effector T cells in chronic infection","volume":"200","author":"Ibitokou","year":"2018","journal-title":"J. Immunol."},{"key":"2025030418133395100_r39","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nature13324","article-title":"Mfsd2a is critical for the formation and function of the blood-brain barrier","volume":"509","author":"Ben-Zvi","year":"2014","journal-title":"Nature"},{"key":"2025030418133395100_r40","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"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/203\/1\/117\/62171709\/ji1801585.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/203\/1\/117\/62171709\/ji1801585.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T20:17:19Z","timestamp":1741119439000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/203\/1\/117\/7952247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1801585","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7]]},"published":{"date-parts":[[2019,7,1]]}}}