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Calcitriol Modulates the CD46 Pathway in T Cells 英文参考文献
CalcitriolModulatestheCD46PathwayinTCells
KarolineKickler1,SiobhanNiChoileain1,2,AnnaWilliams2,AnnaRichards1,AnneL.Astier1,2*
1MRCCentreforInflammationResearch,UniversityofEdinburgh,Queen’sMedicalResearchInstitute,Edinburgh,UnitedKingdom,2MultipleSclerosisResearchCentre,
MRCCentreforRegenerativeMedicine,TheUniversityofEdinburgh,EdinburghBioquarter,Edinburgh,UnitedKingdom
Abstract
ThecomplementregulatorCD46isacostimulatorymoleculeforhumanTcellsthatinducesaregulatoryTr1phenotype,
characterizedbylargeamountsofIL-10secretion.SecretionofIL-10uponCD46costimulationislargelyimpairedinTcells
frompatientswithmultiplesclerosis(MS).VitaminDcanexertadirecteffectonTcells,andmaybebeneficialinseveral
pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)2D or calcitriol) could
3
modulatetheCD46pathwayandrestore IL-10productionbyCD46-costimulated CD4+Tcells frompatients withMS.In
healthyTcells,calcitriolprofoundlyaffectsthephenotypeofCD46-costimulatedCD4+Tcells,byincreasingtheexpression
ofCD28,CD25,CTLA-4andFoxp3whileitconcomitantlydecreasedCD46expression.SimilartrendswereobservedinMS
CD4+TcellsexceptforCD25forwhichastrikingoppositeeffectwasobserved:whileCD25wasnormallyinducedonMST
cellsbyCD46costimulation,additionofcalcitriolconsistentlyinhibiteditsinduction.DespitetheaberranteffectonCD25
expression,calcitriolincreasedtheIL-10:IFNcratio,characteristicoftheCD46-inducedTr1phenotype,inbothTcellsfrom
healthydonorsandpatientswithMS.Hence,weshowthatcalcitriolaffectstheCD46pathway,andthatitpromotesanti-
inflammatoryresponsesmediatedbyCD46.Moreover,itmightbebeneficialforTcellresponsesinMS.
Citation:KicklerK,NiChoileainS,WilliamsA,RichardsA,AstierAL(2012)CalcitriolModulatestheCD46PathwayinTCells.PLoSONE7(10):e48486.doi:10.1371/
journal.pone.0048486
Editor:PabloVilloslada,InstituteBiomedicalResearchAugustPiSunyer(IDIBAPS)–HospitalClinicofBarcelona,Spain
ReceivedJuly12,2012;AcceptedOctober2,2012;PublishedOctober29,2012
Copyright: ? 2012 Kickler e
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