Δ9‐Tetrahydrocannabinol‐mediated epigenetic modifications elicit myeloid‐derived suppressor cell activation via STAT3/S100A8

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

关键词: DNA methylation;    T cell suppression;    arginase 1;    cannabinoid;   

DOI  :  10.1189/jlb.1A1014-479R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

MDSCsarepotentimmunosuppressivecellsthatareinducedduringinflammatoryresponses,aswellasbycancers,toevadetheanti‐tumorimmunity.WerecentlydemonstratedthatmarijuanacannabinoidsarepotentinducersofMDSCs.Inthecurrentstudy,weinvestigatedtheepigeneticmechanismsthroughwhichTHC,anexogenouscannabinoid,inducesMDSCsandcomparedsuchMDSCswiththenai¨veMDSCsfoundinBMofBL6(WT)mice.AdministrationofTHCintoWTmicecausedincreasedmethylationatthepromoterregionofDNMT3aandDNMT3binTHC‐inducedMDSCs,whichcorrelatedwithreducedexpressionofDNMT3aandDNMT3b.Furthermore,promoterregionmethylationwasdecreasedatArg1andSTAT3inTHC‐inducedMDSCs,andconsequently,suchMDSCsexpressedhigherlevelsofArg1andSTAT3.Inaddition,THC‐inducedMDSCssecretedelevatedlevelsofS100A8,acalcium‐bindingproteinassociatedwithaccumulationofMDSCsincancermodels.NeutralizationofS100A8byuseofanti‐S100A8(8H150)invivoreducedtheabilityofTHCtotriggerMDSCs.Interestingly,theelevatedS100A8expressionalsopromotedthesuppressivefunctionofMDSCs.Together,thecurrentstudydemonstratesthatTHCmediatesepigeneticchangestopromoteMDSCdifferentiationandfunctionandthatS100A8playsacriticalroleinthisprocess...

【 授权许可】

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