{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:58:02Z","timestamp":1790661482398,"version":"4.1.0"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,6,18]],"date-time":"2018-06-18T00:00:00Z","timestamp":1529280000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI127654 and R01 AR065807"],"award-info":[{"award-number":["R01 AI127654 and R01 AR065807"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2018.01347","type":"journal-article","created":{"date-parts":[[2018,6,18]],"date-time":"2018-06-18T12:20:09Z","timestamp":1529324409000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":101,"title":["Metabolic Reprogramming and Longevity of Tissue-Resident Memory T Cells"],"prefix":"10.3389","volume":"9","author":[{"given":"Youdong","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Kupper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1146\/annurev.immunol.22.012703.104702","article-title":"Central memory and effector memory T cell subsets: function, generation, and maintenance","volume":"22","author":"Sallusto","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/ni.1718","article-title":"Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus","volume":"10","author":"Gebhardt","year":"2009","journal-title":"Nat Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1084\/jem.20090858","article-title":"Dynamic T cell migration program provides resident memory within intestinal epithelium","volume":"207","author":"Masopust","year":"2010","journal-title":"J Exp Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nature10851","article-title":"Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity","volume":"483","author":"Jiang","year":"2012","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nri.2015.3","article-title":"Tissue-resident memory T cells: local specialists in immune defence","volume":"16","author":"Mueller","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/nm.3883","article-title":"The emerging role of resident memory T cells in protective immunity and inflammatory disease","volume":"21","author":"Park","year":"2015","journal-title":"Nat Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1126\/science.1254803","article-title":"T cell memory. Skin-resident memory CD8(+) T cells trigger a state of tissue-wide pathogen alert","volume":"346","author":"Ariotti","year":"2014","journal-title":"Science"},{"key":"B8","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1126\/science.1257530","article-title":"T cell memory. A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells","volume":"346","author":"Iijima","year":"2014","journal-title":"Science"},{"key":"B9","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1126\/science.1254536","article-title":"T cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses","volume":"346","author":"Schenkel","year":"2014","journal-title":"Science"},{"key":"B10","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/nm.2078","article-title":"Epidermal injury and infection during poxvirus immunization is crucial for the generation of highly protective T cell-mediated immunity","volume":"16","author":"Liu","year":"2010","journal-title":"Nat Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.09.042","article-title":"Staged development of long-lived T-cell receptor alphabeta TH17 resident memory T-cell population to Candida albicans after skin infection","author":"Park","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1007\/s13365-013-0189-3","article-title":"Immunological control of herpes simplex virus infections","volume":"19","author":"Egan","year":"2013","journal-title":"J Neurovirol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"13346","DOI":"10.1038\/ncomms13346","article-title":"CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2","volume":"7","author":"Shin","year":"2016","journal-title":"Nat Commun"},{"key":"B14","doi-asserted-by":"publisher","first-page":"186","DOI":"10.4049\/jimmunol.1700145","article-title":"Bolstering the number and function of HSV-1-specific CD8(+) effector memory T cells and tissue-resident memory T cells in latently infected trigeminal ganglia reduces recurrent ocular herpes infection and disease","volume":"199","author":"Khan","year":"2017","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.it.2015.07.002","article-title":"Tissue instruction for migration and retention of TRM cells","volume":"36","author":"Iijima","year":"2015","journal-title":"Trends Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1172\/JCI96957","article-title":"Influenza-specific lung-resident memory T cells are proliferative and polyfunctional and maintain diverse TCR profiles","volume":"128","author":"Pizzolla","year":"2018","journal-title":"J Clin Invest"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aam6970","article-title":"Resident memory CD8(+) T cells in the upper respiratory tract prevent pulmonary influenza virus infection","volume":"2","author":"Pizzolla","year":"2017","journal-title":"Sci Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"233","DOI":"10.4049\/jimmunol.1602051","article-title":"Lung CD4 tissue-resident memory T cells mediate adaptive immunity induced by previous infection of mice with Bordetella pertussis","volume":"199","author":"Wilk","year":"2017","journal-title":"J Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/S0074-7696(06)50006-3","article-title":"Cell biology of T cell activation and differentiation","volume":"250","author":"Santana","year":"2006","journal-title":"Int Rev Cytol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.molimm.2015.07.036","article-title":"T cell metabolic reprogramming and plasticity","volume":"68","author":"Slack","year":"2015","journal-title":"Mol Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.cell.2017.04.004","article-title":"Metabolic instruction of immunity","volume":"169","author":"Buck","year":"2017","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.3389\/fimmu.2017.01311","article-title":"Sugar or fat? Metabolic requirements for immunity to viral infections","volume":"8","author":"Shehata","year":"2017","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/imm.12655","article-title":"T-cell metabolism governing activation, proliferation and differentiation; a modular view","volume":"150","author":"Dimeloe","year":"2017","journal-title":"Immunology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3142","DOI":"10.1016\/j.celrep.2016.11.065","article-title":"Anabolism-associated mitochondrial stasis driving lymphocyte differentiation over self-renewal","volume":"17","author":"Adams","year":"2016","journal-title":"Cell Rep"},{"key":"B25","doi-asserted-by":"publisher","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":"B26","doi-asserted-by":"publisher","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":"B27","doi-asserted-by":"publisher","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","volume":"41","author":"O\u2019Sullivan","year":"2014","journal-title":"Immunity"},{"key":"B28","doi-asserted-by":"publisher","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":"B29","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1126\/science.176.4032.309","article-title":"Deficient activity of hepatic acid lipase in cholesterol ester storage disease","volume":"176","author":"Burke","year":"1972","journal-title":"Science"},{"key":"B30","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/S0022-2275(20)32518-9","article-title":"New lysosomal acid lipase gene mutants explain the phenotype of Wolman disease and cholesteryl ester storage disease","volume":"39","author":"Pagani","year":"1998","journal-title":"J Lipid Res"},{"key":"B31","first-page":"3","article-title":"The skin as an organ of immunity","volume":"107","author":"Bos","year":"1997","journal-title":"Clin Exp Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"269rv1","DOI":"10.1126\/scitranslmed.3010641","article-title":"Resident memory T cells in human health and disease","volume":"7","author":"Clark","year":"2015","journal-title":"Sci Transl Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"4431","DOI":"10.4049\/jimmunol.176.7.4431","article-title":"The vast majority of CLA+ T cells are resident in normal skin","volume":"176","author":"Clark","year":"2006","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"279ra39","DOI":"10.1126\/scitranslmed.3010302","article-title":"Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells","volume":"7","author":"Watanabe","year":"2015","journal-title":"Sci Transl Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"4031","DOI":"10.1172\/JCI93396","article-title":"Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing alphabeta T cell clones","volume":"127","author":"Matos","year":"2017","journal-title":"J Clin Invest"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aam6346","article-title":"Resident memory T cells in the skin mediate durable immunity to melanoma","volume":"2","author":"Malik","year":"2017","journal-title":"Sci Immunol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.jid.2017.08.038","article-title":"Vitiligo skin is imprinted with resident memory CD8 T cells expressing CXCR3","volume":"138","author":"Boniface","year":"2018","journal-title":"J Invest Dermatol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"53","DOI":"10.4161\/derm.3.2.14816","article-title":"Role of fatty acid transporters in epidermis: implications for health and disease","volume":"3","author":"Khnykin","year":"2011","journal-title":"Dermatoendocrinol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.immuni.2015.04.016","article-title":"Epidermal fatty acid binding protein promotes skin inflammation induced by high-fat diet","volume":"42","author":"Zhang","year":"2015","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nature21379","article-title":"Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism","volume":"543","author":"Pan","year":"2017","journal-title":"Nature"},{"key":"B41","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1038\/nrendo.2015.122","article-title":"Metabolic functions of FABPs \u2013 mechanisms and therapeutic implications","volume":"11","author":"Hotamisligil","year":"2015","journal-title":"Nat Rev Endocrinol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1016\/j.bbalip.2016.03.018","article-title":"The role of CD36 in the regulation of myocardial lipid metabolism","volume":"1861","author":"Kim","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"B43","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1021\/acs.biochem.6b00945","article-title":"Biochemical analysis of the lipoprotein lipase truncation variant, LPL(S447X), reveals increased lipoprotein uptake","volume":"56","author":"Hayne","year":"2017","journal-title":"Biochemistry"},{"key":"B44","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.bbabio.2010.10.022","article-title":"Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells","volume":"1807","author":"Pike","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"B45","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.ctrv.2018.02.004","article-title":"Targeting the microenvironment in solid tumors","volume":"65","author":"Belli","year":"2018","journal-title":"Cancer Treat Rev"},{"key":"B46","doi-asserted-by":"publisher","first-page":"3967","DOI":"10.1073\/pnas.0611618104","article-title":"CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma","volume":"104","author":"Sharma","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e1134412","DOI":"10.1080\/2162402X.2015.1134412","article-title":"The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder","volume":"5","author":"Baras","year":"2016","journal-title":"Oncoimmunology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.3389\/fimmu.2017.01412","article-title":"Immune checkpoint molecules on tumor-infiltrating lymphocytes and their association with tertiary lymphoid structures in human breast cancer","volume":"8","author":"Solinas","year":"2017","journal-title":"Front Immunol"},{"key":"B49","first-page":"12","article-title":"Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human glioma","volume":"7","author":"Dunn","year":"2007","journal-title":"Cancer Immun"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e88955","DOI":"10.1172\/jci.insight.88955","article-title":"Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells","volume":"1","author":"Boddupalli","year":"2016","journal-title":"JCI Insight"},{"key":"B51","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"15221","DOI":"10.1038\/ncomms15221","article-title":"Induction of resident memory T cells enhances the efficacy of cancer vaccine","volume":"8","author":"Nizard","year":"2017","journal-title":"Nat Commun"},{"key":"B53","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.4049\/jimmunol.1402711","article-title":"CD8+CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients","volume":"194","author":"Djenidi","year":"2015","journal-title":"J Immunol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1038\/ni.3775","article-title":"Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer","volume":"18","author":"Ganesan","year":"2017","journal-title":"Nat Immunol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e1358841","DOI":"10.1080\/2162402X.2017.1358841","article-title":"Tissue-resident memory T cells play a key role in the efficacy of cancer vaccines","volume":"6","author":"Granier","year":"2017","journal-title":"Oncoimmunology"},{"key":"B56","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/bjc.2016.412","article-title":"Tumour microenvironment factors shaping the cancer metabolism landscape","volume":"116","author":"Anastasiou","year":"2017","journal-title":"Br J Cancer"},{"key":"B57","doi-asserted-by":"publisher","first-page":"E46","DOI":"10.3390\/vaccines4040046","article-title":"Tumor microenvironment metabolism: a new checkpoint for anti-tumor immunity","volume":"4","author":"Scharping","year":"2016","journal-title":"Vaccines (Basel)"},{"key":"B58","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.ccell.2017.08.004","article-title":"Enhancing CD8(+) T cell fatty acid catabolism within a metabolically challenging tumor microenvironment increases the efficacy of melanoma immunotherapy","volume":"32","author":"Zhang","year":"2017","journal-title":"Cancer Cell"},{"key":"B59","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.cell.2013.12.012","article-title":"What we talk about when we talk about fat","volume":"156","author":"Rosen","year":"2014","journal-title":"Cell"},{"key":"B60","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.cmet.2016.04.011","article-title":"Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk","volume":"23","author":"Stern","year":"2016","journal-title":"Cell Metab"},{"key":"B61","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.smim.2015.10.005","article-title":"Immunological contributions to adipose tissue homeostasis","volume":"27","author":"DiSpirito","year":"2015","journal-title":"Semin Immunol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.cell.2015.02.022","article-title":"Immune regulation of metabolic homeostasis in health and disease","volume":"161","author":"Brestoff","year":"2015","journal-title":"Cell"},{"key":"B63","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/nature14115","article-title":"Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity","volume":"519","author":"Brestoff","year":"2015","journal-title":"Nature"},{"key":"B64","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/nature08636","article-title":"Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells","volume":"463","author":"Moro","year":"2010","journal-title":"Nature"},{"key":"B65","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.immuni.2009.03.014","article-title":"Omental milky spots develop in the absence of lymphoid tissue-inducer cells and support B and T cell responses to peritoneal antigens","volume":"30","author":"Rangel-Moreno","year":"2009","journal-title":"Immunity"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1016\/j.immuni.2017.11.009","article-title":"White adipose tissue is a reservoir for memory T cells and promotes protective memory responses to infection","volume":"47","author":"Han","year":"2017","journal-title":"Immunity"},{"key":"B67","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/j.ijcard.2015.11.060","article-title":"Rationale and benefits of trimetazidine by acting on cardiac metabolism in heart failure","volume":"203","author":"Lopatin","year":"2016","journal-title":"Int J Cardiol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.immuni.2013.04.001","article-title":"The immune system as a sensor of the metabolic state","volume":"38","author":"Odegaard","year":"2013","journal-title":"Immunity"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1038\/ni.2744","article-title":"The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin","volume":"14","author":"Mackay","year":"2013","journal-title":"Nat Immunol"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1016\/j.immuni.2015.11.008","article-title":"T-box transcription factors combine with the cytokines TGF-beta and IL-15 to control tissue-resident memory T cell fate","volume":"43","author":"Mackay","year":"2015","journal-title":"Immunity"},{"key":"B71","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1126\/science.aad2035","article-title":"Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes","volume":"352","author":"Mackay","year":"2016","journal-title":"Science"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1038\/ni.2745","article-title":"Transcriptional downregulation of S1pr1 is required for the establishment of resident memory CD8+ T cells","volume":"14","author":"Skon","year":"2013","journal-title":"Nat Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2018.01347\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T22:01:23Z","timestamp":1661464883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2018.01347\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,18]]},"references-count":72,"alternative-id":["10.3389\/fimmu.2018.01347"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2018.01347","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,18]]},"article-number":"1347"}}