Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function

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

关键词: inflammation;    M1 activation;    M2 activation;    inducible nitric oxide synthase;    arginase I;    Brugia malayi ;   

DOI  :  10.1189/jlb.1110644

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Macrophagesbecomeactivatedbytheirenvironmentanddeveloppolarizedfunctions:classicallyactivated(M1)macrophageseliminatepathogensbutcancausetissueinjury,whereasalternativelyactivated(M2)macrophagespromotehealingandrepair.Mechanismsdirectingpolarizedactivation,especiallyinvivo,arenotunderstoodcompletely,andhere,weexaminedtheroleofSOCSproteins.M2macrophagesactivatedinvitroorelicitedbyimplantingmicei.p.withtheparasiticnematodeBrugiamalayidisplayaselectiveandIL‐4‐dependentup‐regulationofSOCS1butnotSOCS3.UsingsiRNA‐targetedknockdowninBMDM,werevealthattheenhancedSOCS1iscrucialforIL‐4‐inducedM2characteristics,includingahigharginaseI:iNOSactivityratio,suppressionofTcellproliferation,attenuatedresponsestoIFN‐γ/LPS,andcurtailedSOCS3expression.Importantly,SOCS1wasessentialinsustainingtheenhancedPI3KactivitythatdrivesM2activation,defininganewregulatorymechanismbywhichSOCS1controlsM2polarization.Bycontrast,forM1macrophages,SOCS1wasnotonlyanimportantregulatorofproinflammatorymediators(IL‐6,IL‐12,MHCclassII,NO),butcritically,forM1,weshowthatSOCS1alsorestrictedIL‐10secretionandarginaseIactivity,whichotherwisewouldlimittheefficiencyofM1macrophageproinflammatoryresponses.Together,ourresultsuncoverSOCS1,notonlyasafeedbackinhibitorofinflammationbutalsoasacriticalmolecularswitchthattuneskeysignalingpathwaystoeffectivelyprogramdifferentsidesofthemacrophagebalance...

【 授权许可】

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