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1、PosttranscriptionalControlofTCellEffectorFunctionbyAerobicGlycolysisChih-HaoChang,1JonathanD.Curtis,1LeonardB.Maggi,Jr.,2BrandonFaubert,3AlejandroV.Villarino,4DavidOSullivan,1StanleyChing-ChengHuang,1GerritjeJ.W.vanderWindt,1JuliannaBlagih,3JingQiu,1JasonD.Weber,2EdwardJ.Pearce,1RussellG.Jones,3and
2、ErikaL.Pearce1,*1DepartmentofPathology&Immunology2DivisionofMolecularOncology,BRIGHTInstituteWashingtonUniversitySchoolofMedicine,St.Louis,MO63110,USA3GoodmanCancerResearchCentre,DepartmentofPhysiology,McGillUniversity,Montreal,QCH3G1Y6,Canada4NationalInstituteofArthritisandMusculoskeletalandSkinDi
3、seases,NationalInstitutesofHealth,Bethesda,MD20892,USA*Correspondence:erikapearce@path.wustl.eduhttp://dx.doi.org/10.1016/j.cell.2013.05.016SUMMARYlessefficient,indicatingthatitmightprovideotheradvantagesduringproliferation.Itisthoughtthatthemetabolismofprolifer-Aswitchfromoxidativephosphorylationat
4、ingcellsisadaptedtofacilitateuptakeandincorporationof(OXPHOS)toaerobicglycolysisisahallmarkofnutrientsintothebiomassneededtoproduceadaughtercell;Tcellactivationandisthoughttoberequiredtoi.e.,aerobicglycolysisisnecessary,bothintermsofenergymeetthemetabolicdemandsofproliferation.How-andbiosynthesis,f
5、orcellularproliferation(LuntandVanderever,whyproliferatingcellsadoptthislessefficientHeiden,2011;VanderHeidenetal.,2009).However,cellssuchasdendriticcellsswitchfromOXPHOStoaerobicglycolysismetabolism,especiallyinanoxygen-repleteenviron-uponTLR-inducedactivationbutdonotproliferate(Krawczykment,remain
6、sincompletelyunderstood.Weshowetal.,2010).Thisobservationsuggeststhataerobicglycolysisherethataerobicglycolysisisspecificallyrequiredmaybenecessaryforpathwaysotherthan,orinadditionto,foreffectorfunctioninTcellsbutthatthispathwaythoseunderlyingproliferation.Therefore,wesoughttounravelisnotnecessaryfo
7、rproliferationorsurvival.WhentherequirementsforOXPHOSandaerobicglycolysisinTcellactivatedTcellsareprovidedwithcostimulationactivation,proliferation,andeffectorfunction.andgrowthfactorsbutareblockedfromengag
