Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Enhanced Toll‐like receptor (TLR) responses of TNFR‐associated factor 3 (TRAF3)‐deficient B lymphocytes | |
关键词: lymphocyte activation; innate immunity; signal transduction; | |
DOI : 10.1189/jlb.0111044 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
ThekeyroleofTRAF6inTLRsignalingpathwaysiswellknown.MorerecentevidencehasimplicatedTRAF3asanotherTRAFfamilymemberimportanttocertainTLRresponsesofmyeloidcells.PreviousstudiesdemonstratethatTRAF3functionsarehighlycontext‐dependent,displayingreceptorandcell‐typespecificity.WethusexaminedtheTLRresponsesofTRAF3−/−mouseBlymphocytestotestthehypothesisthatTRAF3playsdistinctrolesinsuchresponses,dependingoncelltype.TRAF3−/−DCareknowntohaveadefectintype1IFNproductionandhere,showeddiminishedproductionofTNFandIL‐10andunalteredIL‐6.Inmarkedcontrast,TRAF3−/−BcellsmadeelevatedamountsofTNFandIL‐6protein,aswellasIL‐10andIP‐10mRNA,inresponsetoTLRligands.Also,incontrasttoTRAF3−/−DC,thetype1IFNpathwaywaselevatedinTRAF3−/−Bcells.IncreasedearlyresponsesofTRAF3−/−BcellstoTLRsignalswereindependentofcellsurvivalorproliferationbutassociatedwithelevatedcanonicalNF‐κBactivation.Additionally,TRAF3−/−BcellsdisplayedenhancedTLR‐mediatedexpressionofAIDandIgisotypeswitching.Thus,TRAF3playsvariedandcelltype‐specific,biologicalrolesinTLRresponses...
【 授权许可】
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