Isobel Franks
In humans, the immune response to HBV is age dependent; adults tend to clear the virus, whereas children are more likely to develop chronic infection. From the results of their recent study, Jody Baron and colleagues speculate that interleukin (IL)-21 has a key role in this age-dependent response.
Studying the early immune events of HBV infection in humans is difficult. Baron and her colleagues have developed a mouse model of HBV infection in which differences in viral clearance accurately reflect that seen in humans—young mice fail to clear HBV antigens but adult mice exhibit a robust immune response.
Data from this mouse model show that IL-21 seems to have an important role in determining the immune response to HBV. Adult mice with HBV infection demonstrated increased production of IL-21 in the liver compared with young mice. Furthermore, in adult mice lacking the IL-21 receptor, HBV antigens were able to persist, and these mice had an immune response similar to that seen in the young mice. In humans, IL-21 mRNA levels were increased in patients with acute infection who cleared the virus compared with patients who did not clear the virus.
“We plan to use the model to further understand the differences in the immune responses primed in the young mice as compared to the adult mice, and to identify the cellular and molecular mechanisms that underpin these different immune priming events and different disease outcomes,” concludes Baron. “These studies will identify new potential therapeutic targets to treat HBV infection.”
Publicover, J. et al. IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B. J. Clin. Invest. doi: 10.1172/JCI44198
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