| Human BDCA3(+) dendritic cells are a potent producer of IFN-λ in response to hepatitis C virus. | |
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MedLine Citation:
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PMID: 23213063 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The polymorphisms in IL-28B (IFN-λ3) gene are strongly associated with the efficacy of HCV clearance. Dendritic cells (DCs) sense HCV and produce IFNs, thereby playing some cooperative roles with HCV-infected hepatocytes in the induction of interferon-stimulated genes (ISGs). BDCA3(+) DCs are discovered as a producer of IFN-λ upon toll-like receptor3(TLR3) agonist. We thus aimed to clarify the roles of BDCA3(+) DCs inanti-HCV innate immunity.Seventy healthy subjects and 20 patients with liver tumors were enrolled. BDCA3(+) DCs, in comparison with plasmacytoid DCs and myeloid DCs, were stimulated with TLR agonists, cell-cultured HCV (HCVcc) or Huh7.5.1 cells transfected with HCV/JFH-1. BDCA3(+) DCs were treated with anti-CD81 antibody, inhibitors for endosome acidification, TRIF-specific inhibitor or ultraviolet-irradiated HCVcc. The amounts of IL-29/IFN-λ1, IL-28A/IFN-λ2 and IL-28B were quantified by subtype-specific ELISA. The frequency of BDCA3(+) DCs in PBMC was extremely low but higher in the liver. BDCA3(+) DCs recovered from PBMC or the liver released large amounts of IFN-λs, when stimulated with HCVcc or HCV-transfected Huh7.5.1.BDCA3(+) DCs were able to induce ISGs in the co-existing JFH-1-positive Huh7.5.1 cells. The treatments of BDCA3(+) DCs with anti-CD81 antibody, cloroquine or bafilomycinA1 reduced HCVcc-induced IL-28B release, whereas BDCA3(+) DCs comparably produced IL-28B upon replication-defective HCVcc. The TRIF-specific inhibitor reduced IL-28B release from HCVcc-stimulated BDCA3(+) DCs. In response to HCVcc or JFH-1-Huh7.5.1, BDCA3(+) DCs in healthy subjects with IL-28B major (rs8099917, TT) released more IL-28B than those with IL-28B minor genotype (TG). Conclusion: Human BDCA3(+) DCs,having tendency of being accumulated in the liver, recognize HCV by a CD81-, endosome- and TRIF-dependent manner and produce substantial amounts of IL-28B/IFN-λ3,the ability of which is superior in subjects with IL-28B major genotype. (HEPATOLOGY 2012.). |
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Authors:
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Sachiyo Yoshio; Tatsuya Kanto; Shoko Kuroda; Tokuhiro Matsubara; Koyo Higashitani; Naruyasu Kakita; Hisashi Ishida; Naoki Hiramatsu; Hiroaki Nagano; Masaya Sugiyama; Kazumoto Murata; Takasuke Fukuhara; Yoshiharu Matsuura; Norio Hayashi; Masashi Mizokami; Tetsuo Takehara |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-5 |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: - ISSN: 1527-3350 ISO Abbreviation: Hepatology Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 American Association for the Study of Liver Diseases. |
Affiliation:
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Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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