Dexamethasone potentiates myeloid‐derived suppressor cell function in prolonging allograft survival through nitric oxide

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

关键词: innate immunity;    graft rejection;    tolerance;    Th1 cells;    Tregs ;    glucocorticoids;   

DOI  :  10.1189/jlb.2HI1113-611RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

WhereasGCshavebeendemonstratedtobebeneficialfortransplantationpatients,thepharmacologicalmechanismsremainunknown.Herein,theroleofGRsignalingwasinvestigatedviaapharmacologicalapproachinamurineallogeneicskintransplantationmodel.TheGCDex,arepresentativeGC,significantlyrelievedallograftrejection.InDex‐treatedallograftrecipientmice,CD11b+Gr1+MDSCsprolongedgraftsurvivalandactedasfunctionalsuppressiveimmunemodulatorsthatresultedinfewerIFN‐γ‐producingTh1cellsandagreaternumberofIL‐4‐producingTh2cells.Inagreement,Dex‐treatedMDSCspromotedreciprocaldifferentiationbetweenTh1andTh2invivo.Importantly,theGRisrequiredintheDex‐inducedMDSCeffects.TheblockingofGRwithRU486significantlydiminishedtheexpressionofCXCR2andtherecruitmentofCD11b+Gr1+MDSCs,therebyrecoveringtheincreasedMDSC‐suppressiveactivityinducedbyDex.Mechanistically,DextreatmentinducedMDSCiNOSexpressionandNOproduction.PharmacologicinhibitionofiNOScompletelyeliminatedtheMDSC‐suppressivefunctionandtheeffectsonTcelldifferentiation.ThisstudyshowsMDSCstobeanessentialcomponentintheprolongationofallograftsurvivalfollowingDexorRU486treatment,validatingtheGC–GR–NOsignalingaxisasapotentialtherapeutictargetintransplantation...

【 授权许可】

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