PMID- 30938456 OWN - NLM STAT- MEDLINE DCOM- 20200622 LR - 20200622 IS - 1527-3350 (Electronic) IS - 0270-9139 (Linking) VI - 70 IP - 1 DP - 2019 Jul TI - Characteristics of Impaired Dendritic Cell Function in Patients With Hepatitis B Virus Infection. PG - 25-39 LID - 10.1002/hep.30637 [doi] AB - 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. CI - (c) 2019 by the American Association for the Study of Liver Diseases. FAU - Yonejima, Atsushi AU - Yonejima A AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Mizukoshi, Eishiro AU - Mizukoshi E AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Tamai, Toshikatsu AU - Tamai T AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Nakagawa, Hidetoshi AU - Nakagawa H AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Kitahara, Masaaki AU - Kitahara M AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Yamashita, Tatsuya AU - Yamashita T AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Arai, Kuniaki AU - Arai K AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Terashima, Takeshi AU - Terashima T AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Iida, Noriho AU - Iida N AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Fushimi, Kazumi AU - Fushimi K AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Okada, Hikari AU - Okada H AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Yamashita, Taro AU - Yamashita T AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Sakai, Yoshio AU - Sakai Y AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Honda, Masao AU - Honda M AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. FAU - Kaneko, Shuichi AU - Kaneko S AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa City, Japan. LA - eng GR - JP16fk0310508/AMED/International GR - JP19fk0310107/AMED/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190524 PL - United States TA - Hepatology JT - Hepatology (Baltimore, Md.) JID - 8302946 SB - IM MH - Adult MH - Aged MH - Case-Control Studies MH - Dendritic Cells/*metabolism MH - Female MH - Gene Expression Profiling MH - Hepatitis B/*immunology MH - Humans MH - Male MH - Middle Aged MH - T-Lymphocytes, Cytotoxic/physiology EDAT- 2019/04/03 06:00 MHDA- 2020/06/23 06:00 CRDT- 2019/04/03 06:00 PHST- 2018/10/23 00:00 [received] PHST- 2019/03/25 00:00 [accepted] PHST- 2019/04/03 06:00 [pubmed] PHST- 2020/06/23 06:00 [medline] PHST- 2019/04/03 06:00 [entrez] AID - 10.1002/hep.30637 [doi] PST - ppublish SO - Hepatology. 2019 Jul;70(1):25-39. doi: 10.1002/hep.30637. Epub 2019 May 24.