title: Histone deacetylase inhibitor valproic acid affects plasmacytoid dendritic cells phenotype and function.
abstract: OBJECTIVE
  Plasmacytoid dendritic cells (PDC) represent a rare subset of dendritic cells specialized in the production of type I IFN in response to microbial pathogens. Recent data suggested that histone deacetylase (HDAC) inhibitors possess potent immunomodulatory properties both in vitro and in vivo. In this study, we assayed the ability of the HDAC inhibitor, valproic acid (VPA), to influence the phenotype and functional properties of human PDC isolated from peripheral blood.
  
  
  RESULTS
  We showed that VPA inhibited the production of IFN-α and the proinflammatory cytokines TNF-α and IL-6 by CpG-activated PDC. VPA also affected the phenotype of PDC by reducing the expression of costimulatory molecules induced by CpG activation. Moreover, VPA reduced the capacity of CpG-stimulated PDC to promote CD4(+) T cell proliferation and IFN-γ production, while enhancing the proportion of IL-10 positive T cells.
  
  
  CONCLUSIONS
  These results suggest that HDAC inhibition by VPA alters essential human PDC functions, highlighting the need for monitoring immune functions in cancer patients receiving HDAC inhibitors, but also making these drugs attractive therapies in inflammatory, and autoimmune diseases implicating PDC.
authors.affiliation: INSERM UMR1098, Besançon F25020, France; Université de Franche-Comté, Besançon F25000, France; EFS Bourgogne Franche-Comté, F25020 Besançon Cedex, France.
authors.forename: Jessy
authors.initials: J
authors.lastname: Arbez
authors.affiliation: INSERM UMR1098, Besançon F25020, France; Université de Franche-Comté, Besançon F25000, France; EFS Bourgogne Franche-Comté, F25020 Besançon Cedex, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Lamarthée
authors.affiliation: INSERM UMR1098, Besançon F25020, France; Université de Franche-Comté, Besançon F25000, France; EFS Bourgogne Franche-Comté, F25020 Besançon Cedex, France. Electronic address: beatrice.gaugler@efs.sante.fr.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Gaugler
authors.affiliation: INSERM UMR1098, Besançon F25020, France; Université de Franche-Comté, Besançon F25000, France; EFS Bourgogne Franche-Comté, F25020 Besançon Cedex, France; Centre d'Investigation Clinique en Biothérapie CIC 1431, Plateforme de Biomonitoring, FHU INCREASE, Besançon F25020, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saas
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D008991:Monitoring, Physiologic; D009369:Neoplasms / Q000188:drug therapy*; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D015703:Antigens, CD; C408982:CPG-oligonucleotide; D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D018836:Inflammation Mediators; D009838:Oligodeoxyribonucleotides; D014635:Valproic Acid
keywords: Cytokines; HDAC inhibitor; Plasmacytoid dendritic cells