TIPE2 protein negatively mediates restoration of myeloid dendritic cells in patients with chronic hepatitis B

Abstract

Background Hepatitis B virus (HBV) causes persistence in a subgroup of patients and impaired myeloid dendritic cells (mDCs) functions have been observed in these patients, and the effect could be remedied by treatment with interferon-α (IFN-α)-based antiviral therapies. However, the biological functions of mDCs in HBV infection remains largely unexplored. Methods TIPE2 expression in mDCs was analyzed by qRT-PCR, western blot and flow cytometry. The release of cytokines was assessed using enzyme-linked immunosorbent assay (ELISA). Downregulation of TIPE2 expression was constructed via siRNA. Results Our results showed that TIPE2 was significantly increased in mDCs isolated from chronically HBV-infected subjects compared with healthy subjects or patients achieving antiviral treatment of sustained virological responses (SVR). Interestingly, IFN-α treatment could decrease the expression of TIPE2 in mDCs from HBV patients than that untreated patients, SVR patients, or healthy subjects. Moreover, TIPE2 expression in mDCs was decreased in healthy subjects but not HBV patients after stimulating with poly I:C, while the difference could be abrogated by the treatment with IFN-α in vitro. In addition, TIPE2 expression by poly I:C activated mDCs, with or without IFN-α treatment, negatively correlated with the expression of CD86 and CCR7, and the secretion of interleukin-12 (IL-12), but positively associated with the production of IL-10. Finally, downregulation expression of TIPE2 could increase the production of IL-12 and decrease IL-10 secretion in mDCs of chronically HBV-infected individuals. Conclusions Our study suggested that TIPE2 was a crucial factor in negatively mediating innate immune responses during chronic viral infection.