Affordable Access

Publisher Website

IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B.

Authors
Type
Published Article
Journal
Journal of Clinical Investigation
0021-9738
Publisher
American Society for Clinical Investigation
Publication Date
Volume
121
Issue
3
Pages
1154–1162
Identifiers
DOI: 10.1172/JCI44198
PMID: 21393863
Source
Medline

Abstract

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 were greatly increased in blood samples from acutely infected adults who clear the virus. These observations suggest a different model for the dichotomous, age dependent outcome of HBV infection in humans, in which decreased IL-21 production in younger patients may hinder generation of crucial CD8+ T and B cell responses. These findings carry implications for therapeutic augmentation of immune responses to HBV and potentially other persistent liver viruses.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments
F