MERTK as negative regulator of human T cell activation
[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...
[发布日期] [发布机构]
[效力级别] [学科分类] 生理学
[关键词] tolerogenic dendritic cells;suppression;TAM receptors [时效性]
