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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: TRAIL;    cytotoxicity;    IFN‐;    α;    IFN‐;    γ;    STATs;    HCV;   

DOI  :  10.1189/jlb.4A1014-520R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 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...

【 授权许可】

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