CD86
免疫学
CD80
树突状细胞
生物
乙型肝炎病毒
抗原
免疫系统
趋化因子
CD40
T细胞
病毒
细胞毒性T细胞
生物化学
体外
作者
Atsushi Yonejima,Eishiro Mizukoshi,Toshikatsu Tamai,Hidetoshi Nakagawa,Masaaki Kitahara,Tatsuya Yamashita,Kuniaki Arai,Takeshi Terashima,Noriho Iida,Kazumi Fushimi,Hikari Okada,Taro Yamashita,Yoshio Sakai,Masao Honda,Shuichi Kaneko
出处
期刊:Hepatology
[Wiley]
日期:2019-05-24
卷期号:70 (1): 25-39
被引量:31
摘要
Dendritic cells (DCs) are antigen-presenting cells with a central role in host immune response. This study analyzed gene expression and DC function in hepatitis B virus (HBV) patients, functions impaired because of 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 DCs were stained with antibodies against human leukocyte antigen-DR/Lin-1/CD123/CD11c and separated into plasmacytoid DCs (pDCs) and myeloid DCs by fluorescence-activated cell sorting. Using an interferon-gamma enzyme-linked immunospot assay, we analyzed antigen-specific response in HBV-infected patients. Regarding DC function, we analyzed antigen-presenting capacity, cell migration capacity, phagocytic capacity, and cytokine production capacity. DC gene expression was analyzed by microarray to identify genes related to DC function. No difference was found in the number of DCs in peripheral blood between healthy participants and HBV patients. In cell-surface marker analysis, CD80, CD83, CD86, CD40, and C-C motif chemokine receptor 7 expression levels in pDCs were related to the HBV-specific T-cell response. DCs 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, interleukin (IL)-6 signal transducer (IL6ST) expression level positively correlated with DC surface marker expression level. Adjustment of IL6ST expression level in DCs and treatment with oncostatin M resulted in recovery of DC function. Conclusion: IL6ST expression was identified as one cause of decline in DC function in HBV patients. Adjustment of IL6 family cytokine signaling may be useful for recovering reduced DC function in HBV infection.
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