title: HCV J6/JFH1 tilts the capability of myeloid-derived dendritic cells to favor the induction of immunosuppression and Th17-related inflammatory cytokines.
abstract: OBJECTIVE
  How HCV virus affects the function of dendritic cells (DCs) and their ability to induce CD4+ T cell response remains not fully understood. This study was done to elucidate the impact of HCV on the function of DCs and on DC's capability to induce CD4+ T-cell response.
  
  
  METHODS
  Monocyte-derived DCs (MoDCs) were treated with cell-culture HCV (HCVcc). The effects of HCVcc on DC maturation, CD40L-induced DC maturation, and cytokine production and the capacity of DCs to induce Th cytokine production of allogeneic CD4+ T cells were evaluated.
  
  
  RESULTS
  HCVcc exposure increased expression of both IL-6 and IL-10 by MoDCs. HCV-exposed MoDCs also selectively facilitated allogeneic CD4+ T cells to further produce Th17-related cytokines interleukin 1 (IL-1), IL-6, and IL-17A. Pretreatment of IL-17A inhibited HCV production in Huh7.5 cells, suggesting that induction of Th17 cells may be beneficial to host anti-HCV immunity. Paradoxically, induction of IL-10 expression and the failure of HCV-exposed MoDCs to facilitate other Th cell development may hinder the anti-viral immunity.
  
  
  CONCLUSIONS
  This study highlights both the therapeutic potential of IL-17A in treating HCV infection and the cautious consideration of HCV-induced immunosuppression in DC-based therapy.
authors.affiliation: Key Laboratory of Molecular Virology and Immunology Institut Pasteur of Shanghai Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 225 South Chongqing Road, Shanghai, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Fang
authors.forename: Kai
authors.initials: K
authors.lastname: Zhu
authors.forename: Nining
authors.initials: N
authors.lastname: Guo
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Mo
authors.initials: M
authors.lastname: Guan
authors.forename: Chunfu
authors.initials: C
authors.lastname: Yang
authors.forename: Qinsong
authors.initials: Q
authors.lastname: Pan
authors.forename: Ruicheng
authors.initials: R
authors.lastname: Wei
authors.forename: Chunhui
authors.initials: C
authors.lastname: Yang
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Deng
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.forename: Qibin
authors.initials: Q
authors.lastname: Leng
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D019898:Autocrine Communication; D023201:CD40 Ligand / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007156:Immunologic Memory; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D020381:Interleukin-17 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation; D015398:Signal Transduction; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; C508717:IL17A protein, human; D018836:Inflammation Mediators; D020381:Interleukin-17; D023201:CD40 Ligand