Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
MERTK as negative regulator of human T cell activation | |
关键词: tolerogenic dendritic cells; suppression; TAM receptors; | |
DOI : 10.1189/jlb.3A0714-334R | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
TheaimofthisstudywastotestthehypothesiswhetherMERTK,whichisup‐regulatedinhumanDCstreatedwithimmunosuppressiveagents,isdirectlyinvolvedinmodulatingTcellactivation.MERTKisamemberoftheTAMfamilyandcontributestoregulatinginnateimmuneresponsetoACsbyinhibitingDCactivationinanimalmodels.However,whetherMERTKinteractsdirectlywithTcellshasnotbeenaddressed.Here,weshowthatMERTKishighlyexpressedondex‐inducedhumantol‐DCsandparticipatesintheirtolerogeniceffect.NeutralizationofMERTKinallogenicMLR,aswellasautologousDC–Tcellcultures,leadstoincreasedTcellproliferationandIFN‐γproduction.Additionally,weidentifyapreviouslyunrecognizednoncell‐autonomousregulatoryfunctionofMERTKexpressedonDCs.Mer‐Fcprotein,usedtomimicMERTKonDCs,suppressesnai¨veandantigen‐specificmemoryTcellactivation.ThismechanismismediatedbytheneutralizationoftheMERTKligandPROS1.WefindthatMERTKandPROS1areexpressedinhumanTcellsuponTCRactivationanddriveanautocrineproproliferativemechanism.Collectively,theseresultssuggestthatMERTKonDCscontrolsTcellactivationandexpansionthroughthecompetitionforPROS1interactionwithMERTKintheTcells.Inconclusion,thisreportidentifiedMERTKasapotentsuppressorofTcellresponse...
【 授权许可】
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