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

[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...

[学科分类] 生理学

[关键词] allergic disease;parasite;Nippostrongylus brasiliensis;cimetidine;cetirizine;Th2