Altered effector functions of NK cells in chronic hepatitis C are associated with IFNL3 polymorphism

[摘要] Interferonα‐mediatedeffectorfunctionsofNKcellsmaycontributetothecontrolofHCVreplicationandthepathogenesisofliverdisease.Thesingle‐nucleotidepolymorphismrs12979860nearIFNL3(previouslyknownasIL28B)isimportantinresponsetoIFN‐αtreatmentandinspontaneousresolutionofacutehepatitisC.TheroleoftheIFNL3polymorphisminNKcellfunctionisunclear.Thus,weinvestigatedtheroleofIFNL3polymorphismintypeIIFN‐dependentregulationofNKcellfunctionsinpatientswithcHCandhealthycontrolsubjects.WedemonstratedamarkedpolarizationofNKcellstowardcytotoxicityinresponsetoIFN‐αstimulationinpatientswithhepatitisC.ThatTRAILup‐regulationwaspresent,particularlyinpatientswiththeIFNL3‐TTallele,wassupportedbyashiftinthepSTAT‐1:pSTAT‐4ratiostowardpSTAT‐1.InpatientsbearingtheIFNL3‐TTallele,NKcelleffectorfunctioncorrelatedwithliverdiseaseactivity.Incontrast,highercytokineproductionofNKcellswasobservedinhealthyindividualswiththeIFNL3‐CCgenotype,whichmaysupportspontaneousHCVclearanceinacuteinfection.Overall,thesefindingsshowthattheroleofNKcellsmaydifferinchronicinfectionvs.earlyantiviraldefenseandthattheIFNL3genotypedifferentiallyinfluencesNKcellfunction...

[学科分类] 生理学

[关键词] TRAIL;cytotoxicity;IFN‐αIFN‐γSTATs;HCV