Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
GM‐CSF‐induced, bone‐marrow‐derived dendritic cells can expand natural Tregs and induce adaptive Tregs by different mechanisms | |
关键词: T cells; autoimmunity; Foxp3; OX40‐; OX40L; TGF‐; β; | |
DOI : 10.1189/jlb.0310154 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
Inourearlierwork,wehadshownthatGM‐CSFtreatmentofCBA/JmicecansuppressongoingthyroiditisbyinducingtolerogenicCD8α−DCs,whichhelpedexpandand/orinduceCD4+Foxp3+Tregs.ToidentifytheprimarycelltypethatwasaffectedbytheGM‐CSFtreatmentandunderstandthemechanismbywhichTregswereinduced,wecomparedtheeffectofGM‐CSFonmaturedspDCsandBMDCprecursorsinvitro.MaturedspDCsexposedtoGM‐CSFexvivoinducedonlyamodestincreaseinthepercentageofFoxp3‐expressingTcellsincocultures.Incontrast,BMcells,whenculturedinthepresenceofGM‐CSF,gaverisetoapopulationofCD11c+CD11bHiCD8α−DCs(BMDCs),whichwereabletoexpandFoxp3+TregsuponcoculturewithCD4+Tcells.Thiscontact‐dependentexpansionoccurredintheabsenceofTCRstimulationandwasabrogatedbyOX40Lblockage.Additionally,theBMDCssecretedhighlevelsofTGF‐β,whichwasrequiredandsufficientforadaptivedifferentiationofTcellstoFoxp3+Tregs,onlyuponTCRstimulation.TheseresultsstronglysuggestthattheBMDCsdifferentiatedbyGM‐CSFcanexpandnTregsandinduceadaptiveTregsthroughdifferentmechanisms...
【 授权许可】
CC BY
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