Hepatology. 2019 Apr 2. doi: 10.1002/hep.30637. [Epub ahead of print]
Characteristics of impaired dendritic cell function in patients with hepatitis B virus infection.
Yonejima A1, Mizukoshi E1, Tamai T1, Nakagawa H1, Kitahara M1, Yamashita T1, Arai K1, Terashima T1, Iida N1, Fushimi K1, Okada H1, Yamashita T1, Sakai Y1, Honda M1, Kaneko S1.
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Abstract
Dendritic cells are antigen-presenting cells with a central role in host immune response. This study analyzed gene expression and dendritic cell function in hepatitis B virus (HBV) patients, functions impaired due to HBV, and identified the genes related to these functions. Peripheral blood mononuclear cells from 64 HBV patients and 19 healthy controls were analyzed. Peripheral blood dendritic cells were stained with antibodies against HLA-DR/Lin-1/CD123/CD11c and separated into plasmacytoid dendritic cells and myeloid dendritic cells by fluorescence-activated cell sorting. Using IFN-γ enzyme-linked immunospot assay, we analyzed the antigen-specific response in HBV-infected patients. Regarding dendritic cell function, we analyzed antigen-presenting capacity, cell migration capacity, phagocytic capacity, and cytokine production capacity. Dendritic cell gene expression was analyzed by microarray to identify genes related to dendritic cell function. No difference was found in the number of dendritic cells in peripheral blood between healthy participants and HBV patients. In cell surface marker analysis, CD80, CD83, CD86, CD40, and CCR7 expression levels in plasmacytoid dendritic cells were related to the HBV-specific T cell response. Dendritic cells from HBV patients exhibited decreases in antigen-presenting capacity, migration capacity, and cytokine production capacity. In gene expression analysis, immune-related genes with greatly reduced expression levels in chronic hepatitis B patients were identified. Of these genes, IL6ST expression level positively correlated with the dendritic cell surface marker expression level. Adjustment of the IL6ST expression level in dendritic cells and treatment with oncostatin M resulted in recovery of dendritic cell function. CONCLUSION: IL6ST expression was identified as one cause of decline in dendritic cell function in HBV patients. Adjustment of IL6 family cytokine signaling may be useful for recovering reduced dendritic cell function in HBV infection. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
T cell; chronic hepatitis; gp130; immunotherapy; interleukin-6