Jessy Arbez1, Baptiste Lamarthée1, Béatrice Gaugler2, Philippe Saas3. 1. INSERM UMR1098, Besançon F25020, France; Université de Franche-Comté, Besançon F25000, France; EFS Bourgogne Franche-Comté, F25020 Besançon Cedex, France. 2. 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. 3. 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.
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. METHODS AND 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. CONCLUSION: 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.
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. METHODS AND 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. CONCLUSION: These results suggest that HDAC inhibition by VPA alters essential human PDC functions, highlighting the need for monitoring immune functions in cancerpatients receiving HDAC inhibitors, but also making these drugs attractive therapies in inflammatory, and autoimmune diseases implicating PDC.
Authors: Jingjing Ren; Michelle D Catalina; Kristin Eden; Xiaofeng Liao; Kaitlin A Read; Xin Luo; Ryan P McMillan; Matthew W Hulver; Matthew Jarpe; Prathyusha Bachali; Amrie C Grammer; Peter E Lipsky; Christopher M Reilly Journal: Front Immunol Date: 2019-10-25 Impact factor: 7.561
Authors: Øystein Bruserud; Galina Tsykunova; Maria Hernandez-Valladares; Hakon Reikvam; Tor Henrik Anderson Tvedt Journal: Pharmaceuticals (Basel) Date: 2021-05-02