Mast cell histamine promotes the immunoregulatory activity of myeloid‐derived suppressor cells

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

关键词: allergic disease;    parasite;    Nippostrongylus brasiliensis;    cimetidine;    cetirizine;    Th2;   

DOI  :  10.1189/jlb.5A1213-644R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

IthasbeenshownrecentlythatMCsarerequiredfordifferentialregulationoftheimmuneresponsebygranulocyticversusmonocyticMDSCs.GranulocyticMDSCspromotedparasiteclearance,whereasmonocyticMDSCsenhancedtumorprogression;bothactivitieswereabrogatedinMC‐deficientmice.Herein,wedemonstratethatthelackofMCsalsoinfluencesMDSCtrafficking.PreferentialtraffickingtotheliverwasnotseeninMC‐deficientmice.Inaddition,evidencethattheMCmediatorhistaminewasimportantinMDSCtraffickingandactivationisalsoshown.MDSCsexpressHR1–3.BlockadeofthesereceptorsbyHR1orHR2antagonistsreversedthehistamineenhancementofMDSCsurvivalandproliferationobservedincellculture.Inaddition,histaminedifferentiallyinfluencedArg1andiNOSgeneexpressioninMDSCsandgreatlyenhancedIL‐4andIL‐13message,especiallyingranulocyticMDSCs.EvidencethathistamineinfluencedactivityseeninvitrotranslatedtoinvivowhenHR1andHR2antagonistsblockedtheeffectofMDSCsonparasiteexpulsionandtumormetastasis.AllofthesedatasupporttheMDSC‐mediatedpromotionofTh2immunity,leadingtothesuggestionthatallergic‐proneindividualswouldhaveelevatedMDSClevels.ThiswasdirectlydemonstratedbylookingattherelativeMDSClevelsinallergicversuscontrolpatients.MonocyticMDSCstrendedhigher,whereasgranulocyticMDSCswereincreasedsignificantlyinallergicpatients.Takentogether,ourstudiesindicatethatMCsandMC‐releasedhistaminearecriticalforMDSC‐mediatedimmuneregulation,andthisinteractionshouldbetakenintoconsiderationfortherapeuticinterventionsthattargetMDSCs...

【 授权许可】

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