biostudies-literaturePublicover JIntramural NIH HHSNIDDK NIH HHSNIAID NIH HHS1154-62https://www.ebi.ac.uk/biostudies/studies/S-EPMC3049376biostudies-literatureUnknown121(3)HBV is a noncytopathic hepadnavirus and major human pathogen that causes immune-mediated acute and chronic hepatitis. The immune response to HBV antigens is age dependent: viral clearance occurs in most adults, while neonates and children usually develop chronic infection and liver disease. Here, we characterize an animal model for HBV infection that recapitulates the key differences in viral clearance between early life and adulthood and find that IL-21 may be part of an effective primary hepatic immune response to HBV. In our model, adult mice showed higher HBV-dependent IL-21 production in liver, compared with that of young mice. Conversely, absence of the IL-21 receptor in adult mice resulted in antigen persistence akin to that of young mice. In humans, levels of IL-21 transcripts wereThe Journal of clinical investigationIL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B.PMC3049376P30 DK026743T32DK060414P30DK026743T32 DK060414R01AI068090R01 AI068090Spolski RBaron JLPublicover JAvanesyan LNishimura SWang ZEGoodsell ACooper SVilarinho SLeonard WJfalseIL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B.HBV is a noncytopathic hepadnavirus and major human pathogen that causes immune-mediated acute and chronic hepatitis. The immune response to HBV antigens is age dependent: viral clearance occurs in most adults, while neonates and children usually develop chronic infection and liver disease. Here, we characterize an animal model for HBV infection that recapitulates the key differences in viral clearance between early life and adulthood and find that IL-21 may be part of an effective primary hepatic immune response to HBV. In our model, adult mice showed higher HBV-dependent IL-21 production in liver, compared with that of young mice. Conversely, absence of the IL-21 receptor in adult mice resulted in antigen persistence akin to that of young mice. In humans, levels of IL-21 transcripts were2011-01-01T00:00:00Z2011 Mar2025-04-07T00:14:23.295Z2019-03-27T00:39:24ZS-EPMC30493762139386310.1172/jci4419810.1172/JCI44198