mTOR limits the recruitment of CD11b+Gr1+Ly6Chigh myeloid‐derived suppressor cells in protecting against murine immunological hepatic injury

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

关键词: cell migration;    inflammatory cell infiltration;    immune defense;    autoimmune;    inflammation;   

DOI  :  10.1189/jlb.0913473

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThemTORpathwayintegratesdiverseenvironmentalinputs,includingimmunesignalsandmetaboliccues,todirecttheinnateandadaptiveimmuneresponses.MDSCsareaheterogeneouscellpopulationthatplaysacrucialregulatoryeffectinimmune‐relateddiseases.However,whethermTORsignalingaffectsthefunctionsofMDSCsremainslargelyunknown.Here,weshowthatmTORsignalingisapivotalnegativedeterminantofMDSCrecruitmentinIMHdisease.InthecontextofIMH,inhibitionofmTORwithrapamycininCD11b+Gr1+MDSCsmediatesprotectionagainstIMHandservesasafunctional,suppressiveimmunemodulatorthatresultsinincreasedCD11b+Gr1+Ly6ChighMDSCrecruitmenttoinflammatorysites.Inagreementwiththis,mTORdown‐regulationpromotesCD11b+Gr1+Ly6ChighMDSCmigrationinvitroandinvivo.Mechanistically,mTORactivitydown‐regulationinMDSCsinducediNOSexpressionandNOproduction.PharmacologicinhibitionofiNOScompletelyeliminatedMDSCrecruitment.ThisstudyidentifiesMDSCsasanessentialcomponentforprotectionagainstIMHfollowingrapamycintreatment.RapamycintreatmentormTORinhibitionpromotesCD11b+Gr1+Ly6ChighMDSCrecruitmentandiscriticallyrequiredforprotectionagainsthepaticinjury.ThisstudyfurthervalidatesthetargetingofmTORsignalingasapotentialtherapeuticapproachtoIMH‐relateddiseases...

【 授权许可】

CC BY