第九届全国免疫学学术大会

2014-10-18

中国山东济南

Background&Aims:Mature natural killer(NK)cells acquire the ability to defend the host against viral infections.However,excessive response of NK cell to acute viral infection can cause severe tissue damage,and the mechanisms for regulation NK cell response remain to be elucidated.Methods:The polyinosinic:polycytidylic acid(poly I:C)induced acute hepatitis in D-galactosamine(D-GalN)-sensitized livers,mimicking the virus-induced acute liver injury.The roles of IL-17A in NK cell maturation were analyzed using1117a~(-/-)mice,pLIVE-17A and pLIVE-15 vectors.The bone marrow chimeras assay was used to analyze the source of IL-17A in steady state.Results:More severe liver injury and lethality were observed in Il1a~(-/-)mice compared to their wild-type counterparts after the viral double-stranded RNA analog poly I:C challenge.Mechanistically,the genetic deficiency in Il17a generated more terminal mature NK cells in vivo during ontogeny.Accordingly,more IFN-γ-producing NK cells and cytotoxic NK cells were generated in Il17a~(-/-)mice.Long-term over-expression of IL-17A in vivo markedly reduced terminal mature NK cells.Furthermore,IL-17A could suppress IL-15-prormoted NK cell terminal maturation via constraining IL-15-induced STAT5 phosphorylation.Mixed bone marrow chimeras and hematopoietic reconstitution identified that NK cellregulating IL-17A was derived from hematopoietic cells in steady state.Conclusions:IL-17A suppresses NK cell terminal maturation by constraining IL-15 signaling and alleviates viral infection-induced NK cell-mediated fulminant hepatitis.