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Metabolic and epigenetic regulation of T-cell

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ReviewARticlehttps://doi.org/10.1038/s42255-020-00280-91DepartmentofFundamentalOncology,UniversityofLausanne,Lausanne,Switzerland.2LudwigInstituteforCancerResearch,UniversityofLausanne,Epalinges,Switzerland.✉e-mail:yi-ru.yu@unil.ch;ping-chih.ho@unil.chAfterT-cellactivation,naiveCD8+TcellsdifferentiateintoeithereffectorTcellsormemoryTcellsviatranscrip-tionalregulation,inaprocesssupportedbymetabolicreprogrammingtomeetdifferentenergydemands.Forinstance,naiveTcellsinastateofmetabolicquiescenceuseoxidativephosphorylation(OXPHOS)forenergyproduction.Afteracti-vation,naiveTcellsundergoametabolicswitchgovernedbythephosphatidylinositol-3-kinase–proteinkinaseB–mammaliantargetofrapamycin(PI3K–Akt–mTOR)pathway;thisswitchsupportsdifferentiationintoeffectorTcells,whichrelyonaerobicglycoly-sisfortheirrapidexpansionandeffectorfunctions1–4.Incontrast,memoryTcellspersistafterantigenclearanceandhaveadistinctmetabolicprogramcharacterizedbyelevatedOXPHOSandautoph-agy5,6.Beyondmetabolicpreferences,thedynamicsofmitochondriaisintrinsicallylinkedtoT-cellmetabolismtofulfilenergydemandsandimmuneresponseseitherduringcelldifferentiationorunderstressfulconditions.IneffectorTcells,T-cellreceptor(TCR)signal-lingfacilitatesmitochondrialfissionandleadstolowerrespiratoryactivity.Incontrast,memoryTcellscontainrelativelygreatermito-chondrialmass,andthemitochondriahaveafusedultrastructureandarelativelyhighersparerespiratorycapacity(SRC);thesechar-acteristicshavebeensuggestedtosupportthesurvivalofthesecellsintheab

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