IFN‐α promotes rapid human Treg contraction and late Th1‐like Treg decrease

[摘要] TypeIIFNsarepleiotropiccytokinesthatexertconcertedactivitiesinthedevelopmentofantiviralresponses.RegulatoryTcellsrepresentaphysiologiccheckpointinthebalancebetweenimmunityandtolerance,requiringfineandrapidcontrols.Here,weshowthathumanregulatoryTcellsareparticularlysensitivetothesequentialeffectsofIFN‐α.First,IFN‐αexertsarapid,antiproliferativeandproapoptoticeffectinvitroandinvivo,asearlyasafter2dofpegylatedIFN/ribavirintherapyinpatientswithchronichepatitisC.Suchactivitiesresultinthedecline,atd2,incirculatingregulatoryTcellfrequencyandspecificallyoftheactivatedregulatoryTcellsubset.Later,IFN‐basedtherapyrestrainsthefractionofregulatoryTcellsthatcanbepolarizedintoIFN‐γ‐producingTh1‐likeregulatoryTcellsknowntocontributetochronicimmuneactivationintype1inflammation.Indeed,Th1‐likeregulatoryTcellfrequencysignificantlydeclinesafter30doftherapyinvivoinrelationtothepersistentdeclineofrelevantIL‐12sources,namely,myeloidand6‐sulfoLacNAc‐expressingdendriticcells.Thiseventisrecapitulatedbyexperimentsinvitro,providingevidencethatitmaybeattributabletotheinhibitoryeffectofIFN‐αonIL‐12‐induced,Th1‐likeregulatoryTcellpolarization.Insummary,ourresultssuggestthatIFN‐α‐driven,earlyregulatoryTcelldepletioncontributestothedevelopmentofantiviralimmunity,ultimatelyresultingintheresolutionoftype1inflammation...

[学科分类] 生理学

[关键词] STAT;apoptosis;IL‐12;desensitization.