| First Author | Huang MT | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 6 | Pages | 1696-705 |
| PubMed ID | 25820812 | Mgi Jnum | J:229704 |
| Mgi Id | MGI:5753020 | Doi | 10.1002/eji.201445239 |
| Citation | Huang MT, et al. (2015) Feedback regulation of IFN-alpha/beta signaling by Axl receptor tyrosine kinase modulates HBV immunity. Eur J Immunol 45(6):1696-705 |
| abstractText | Hepatitis B virus (HBV) is known to cause age-dependent infection outcomes wherein most infections during young age result in chronicity. The mechanism underlying the differential outcome remains elusive. By using hydrodynamic injection of the replication-competent pAAV-HBV, we established a mouse model in which HBV persistence was generated in 4-5 w/o C57BL/6 young mice, but not in adult mice over 10 w/o. HBV-tolerant young mice expressed higher interferon (IFN)-alpha/beta levels in hepatocytes and intrahepatic plasmacytoid DCs (pDCs) than adult mice after pAAV-HBV injection. Excessive IFN-alpha/beta expression in young mice was associated with induction of the Axl regulatory pathway and expansion of intrahepatic Treg cells. In line with these findings, augmented IFN-beta expression increased Axl expression in the liver and HBV persistence in adult mice, whereas IFN-alpha/beta signaling blockage decreased Axl expression and HBV persistence in young mice. Accordingly, Axl overexpression decreased HBV clearance of adult mice whereas Axl silencing enhanced HBV clearance of young mice. In vitro, IFN-beta priming of pDCs and Axl-overexpressing macrophages enhanced Treg-cell differentiation. These findings suggest that age-dependent HBV chronicity is attributed to IFN-beta-Axl immune regulation, which is selectively induced in young mice by excessive IFN-alpha/beta production at early stage of HBV infection. |
