Background and Aims: Hepatitis B virus (HBV) has been reported to suppress immune function of dendritic cells (DCs). This study investigated DC functions and characteristic gene expression profiles in HBV-infected patients.
Material and Methods: Peripheral blood mononuclear cells (PBMCs) were collected from HBV-infected patients and healthy individuals. PBMCs were labeled with antibodies against HLA-DR, Lin-1, CD123, and CD11c, and fluorescence-activated cell sorting (FACS) was used to sort DCs into plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). To compare DC functions phagocytic activity, migration activity and antigen presenting capacity were measured using a phagocytosis assay kit, cell migration assay and the BrdU Cell Proliferation ELISA Kit. In addition, Extracted mRNAs from FACS-sorted DCs were subjected to gene expression analysis using Affymetrix Human 133U Plus 2.0. Furthermore, the lentiviral plasmid pLVSIN-gp130 was used to modify the expression level of IL6ST in order to clarify how the gene medication affects DC functions and whether the administration of oncostatin M improves DC functions.
Results: Functional analysis of DC cells revealed that phagocytic, migration, and antigen presenting activities tended to be lower in HBV-infected patients than in healthy individuals. Gene expression analysis identified 6 immunologically relevant genes, of which expression levels were decreased markedly in untreated patients with hepatitis B but reverted slightly after treatment. Among these 6 genes, the expression level of the IL-6ST (gp130) gene positively correlated with expression levels of the DC surface markers. Other findings included the modification of IL6ST gene expression and the oncostatin M-induced modification of migration and antigen presenting abilities of DC cells.
Conclusions: We found that HBV infection causes marked changes in DC functions and gene expression levels. Also in patients with chronic hepatitis B, the IL6ST gene is a causal factor of functional decline in DC cells, but administration of oncostatin M improves DC functions.