Δ9‐Tetrahydrocannabinol attenuates allogeneic host‐versus‐graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid‐derived suppressor cells

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

关键词: T cell suppression;    skin allograft;    allograft tolerance;    THC;   

DOI  :  10.1189/jlb.3A0115-030RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Immunecellshavebeenshowntoexpresscannabinoidreceptorsandtoproduceendogenousligands.Moreover,activationofcannabinoidreceptorsonimmunecellshasbeenshowntotriggerpotentimmunosuppression.Despitesuchstudies,theroleofcannabinoidsintransplantation,specificallytopreventallograftrejection,hasnot,toourknowledge,beeninvestigatedpreviously.Inthecurrentstudy,wetestedtheeffectofTHConthesuppressionofHvGDaswellasrejectionofskinallografts.Tothisend,westudiedHvGDbyinjectingH‐2ksplenocytesintoH‐2bmiceandanalyzingtheimmuneresponseinthedrainingingLNs.THCtreatmentsignificantlyreducedTcellproliferationandactivationindrainingLNsoftherecipientmiceanddecreasedearlystagerejection‐indicatorcytokines,includingIL‐2andIFN‐γ.THCtreatmentalsoincreasedtheallogeneicskingraftsurvival.THCtreatmentinHvGDmiceledtoinductionofMDSCs.UsingMDSCdepletionstudiesaswellasadoptivetransferexperiments,wefoundthatTHC‐inducedMDSCswerenecessaryforattenuationofHvGD.Additionally,usingpharmacologicalinhibitorsofCB1andCB2receptorsandCB1andCB2knockoutmice,wefoundthatTHCwasworkingpreferentiallythroughCB1.Together,ourresearchshows,forthefirsttimetoourknowledge,thattargetingcannabinoidreceptorsmayprovideanoveltreatmentmodalitytoattenuateHvGDandpreventallograftrejection...

【 授权许可】

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