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1、ARTICLESSplenicstromadrivesmaturedendriticcellstodifferentiateintoregulatorydendriticcellsMinghuiZhang1,3,HuaTang2,3,ZhenhongGuo1,3,HuazhangAn1,XuejunZhu1,WengangSong1,JunGuo1,XinHuang1,TaoyongChen1,JianliWang2&XuetaoCao1,2Thefatesofdendriticcells(DCs)afterantigenpresentationhavebeenstudie
2、dextensively,buttheinfluenceoflymphoidmicroenvironmentsonDCsismostlyunknown.Here,usingsplenicstromalcellstomimictheimmunemicroenvironment,weshowthatcontactwithstromalcellspromotedmatureDCstoproliferateinafibronectin-dependentwayandthatbothstromalcellcontactandstromalcell–derivedtransformingg
3、rowthfactor-binducedtheirdifferentiationintoanewregulatoryDCsubset.Wehaveidentifiedaninvivocounterpartinthespleenwithsimilarphenotypeandfunctions.ThesedifferentiatedDCssecretedhttp://www.nature.com/natureimmunologynitricoxide,whichmediatedthesuppressionofTcellproliferationinresponsetoantige
4、npresentationbymatureDCs.Thus,ourfindingsidentifyanimportantmechanismbywhichthemicroenvironmentregulatesimmuneresponses.Dendriticcells(DCs)arespecializedantigen-presentingcellsthatareoncell-cellcontactandtransforminggrowthfactor-b(TGF-b).Com-pivotalinimmuneresponses.ThedifferentDCsubsetsand
5、theirparedwithfullymaturedDCs,thesedifferentiatedDCs(diffDCs)hadrespectivefateshavebeenexaminedextensively15.DCsarecommonlylowerexpressionofmajorhistocompatibilitycomplexclassII,CD86consideredtobeterminallydifferentiatedcellsderivedfromhemato-andCD11c,buthigherexpressionofcostimulatorymole
6、culessuchaspoieticprogenitorsormonocytes6,7.Afterantigenuptakeandinflam-CD80,CD40,CD106andCD11b.Theyalsosecretedmoreinterleukinmatorystimulation,immatureDCs(imDCs)inperipheraltissues10(IL-10)andnitricoxide(NO)andlessIL-12andTGF-b.Unlikethebecomematureandmigratetosecondarylymphoidorgans,wher
7、eregulatoryDCsreportedbefore1316,thesedifferentiatedregulatorytheyactivateTcells.ItisgenerallyacceptedthatmatureDCs(maDCs)DCsmaintainedtheabilitytoactivatenaiveTcellsbutdidnotcanundergoactivation-inducedapoptosisafterinteractionwithpromotetheirproliferation.Fu
