MERTK as negative regulator of human T cell activation

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

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】

CC BY