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1、ARTHRITIS&RHEUMATISMVol.58,No.6,June2008,pp1619–1629DOI10.1002/art.23497©2008,AmericanCollegeofRheumatologyCytokinesSecretedinResponsetoToll-likeReceptorLigandStimulationModulateDifferentiationofHumanTh17CellsMichaelG.Kattah,MichaelT.Wong,MatthewD.Yocum,andPaulJ.UtzObjective.Th17cells(
2、interleukin-17[IL-17]–withIL-17–inducingactivity.TcellactivationinthesecretingThelpercells)havebeenimplicatedinthepresenceofrecombinantIL-1,IL-6,andIL-23recon-pathogenesisofrheumatoidarthritisandotherauto-stitutedrobustIL-17production,andthiswasenhancedimmunediseases,butthesolublefact
3、orsthatinfluencebytransforminggrowthfactor(TGF).IL-6sup-humanTh17differentiationhaveyettobefullyeluci-pressedtheexpressionofforkheadboxP3andreverseddated.ThisstudywasundertakentoinvestigatetheTGF-mediatedinhibitionofTcellproliferation,buthypothesisthatthecytokinessecretedbyhumanperi
4、-didnottriggerIL-17secretion.IL-17productionwaspheralbloodmononuclearcells(PBMCs)inresponsetocompletelyabrogatedbyanti–IL-1orIL-1receptorasubsetofToll-likereceptor(TLR)ligandswouldantagonistandpartiallyinhibitedbyanti–IL-6,anti–influenceTh17polarization.IL-2,orexogenousretinoicacid,but
5、notbyanti–tumorMethods.SupernatantsfromhumanPBMCsnecrosisfactor.IL-1andIL-6independentlyinducedtreatedwithapanelofTLRagonistsweretestedforIL-21secretion,butthepresenceofIL-21alonewasnottheirabilitytoinducedenovoIL-17productioninnaivesufficientforIL-17production.Thelpercells.Multiplex
6、cytokineanalysiswasusedtoConclusion.TheseresultsindicatethatligationidentifycandidatecytokinesforsubsequentblockingofasubsetofTLRsgeneratesproinflammatorycyto-andsufficiencyexperiments.kinesthatcombinetopotentiatehumanTh17differ-Results.ConditionedmediafromPBMCsstimu-entiation.latedwit
7、hTLR-4orTLR-8/7agonists,butnotfromthosestimulatedwithTLR-2/1,-3,or-9agonists,evokedrobustsecretionofIL-17byThelpercells,independentTheidentificationoftheTh17subsetofcoculturewithantigen-presentingcells.Multiplex(interleukin-17[IL-17]–secretingThelpercells)asaanalysisof22cytokinesandc
