TSLP directly impairs pulmonary Treg function association with aberrant tolerogenic immunity in asthmatic airway 英文参考文献.docVIP

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TSLP directly impairs pulmonary Treg function association with aberrant tolerogenic immunity in asthmatic airway 英文参考文献.doc

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TSLP directly impairs pulmonary Treg function association with aberrant tolerogenic immunity in asthmatic airway 英文参考文献

Nguyenetal.Allergy,AsthmaClinicalImmunology2010,6:4 /content/6/1/4 ALLERGY, ASTHMA CLINICAL IMMUNOLOGY RESEARCH OpenAccess TSLPdirectlyimpairspulmonaryTregfunction: associationwithaberranttolerogenicimmunityin asthmaticairway KhoaDNguyen,ChristopherVanichsarn,KariCNadeau* Abstract Background:Eventhoughthymicstromallymphopoietin(TSLP)hasbeenimplicatedinthedevelopmentof allergicinflammation,itsinfluenceonimmunetolerancemediatedbyregulatoryTcells(Treg)havenotbeen explored.WeaimedtodissecttheinfluenceofTSLPonimmunosuppressiveactivitiesofTreganditspotential consequencesinhumanallergicasthma. Methods:InvitroculturesystemwasutilizedtostudytheeffectsofTSLPonhumanTreg.Thefunctional competencyofpulmonaryTregfromacohortof15allergicasthmatic,15healthycontrol,and15non-allergic asthmaticsubjectswasalsoevaluatedbysuppressionassaysandflowcytometricanalysis. Results:ActivatedpulmonaryTregexpressedTSLP-RandrespondedtoTSLP-mediatedactivationofSTAT5.TSLP directlyandselectivelyimpairedIL-10productionofTregandinhibitedtheirsuppressiveactivity.Inhumanallergic asthma,pulmonaryTregexhibitedasignificantdecreaseinsuppressiveactivityandIL-10productioncomparedto healthycontrolandnon-allergicasthmaticcounterparts.Thesefunctionalalterationswereassociatedwithelevated TSLPexpressioninbronchoaveolarlavagefluid(BAL)ofallergicasthmaticsubjects.Furthermore,allergicasthmatic BALcouldsuppressIL-10productionbyhealthycontrolpulmonaryTreginaTSLP-dependentmanner. Conclusions:TheseresultsprovidethefirstevidencesforadirectroleofTSLPintheregulationofsuppressive activitiesofTreg.TSLPmediatedinhibitionofTregfunctionmightpresentanovelpathologicmechanismto dampentolerogenicimmuneresponsesininflamedasthmaticairway. Background these evidences strongly suggested TSLP as a positive Thymic stromal lymphopoietin (TSLP) was initially modulatorofTh-2-biasedinflammation. identifiedasbeinginvolvedinlymphocytedevelopment RegulatoryTcells(Treg)haveemergedasakeyregu- [1,2].Subsequently,itwas