Trichostatin A blocks type I interferon production by activated plasmacytoid dendritic cells.
Plasmacytoid dendritic cells (PDC) represent the main type I interferon (IFN-I) producing cells. Emerging evidence supports a role for IFN-I in autoimmune diseases. Given the central role of PDC in the pathogenesis of systemic lupus erythematosus (SLE), we investigated the effect of Trichostatin A (TSA), a prototypic histone deacetylase inhibitor, on PDC activation. TSA inhibited the production of IFN-I, TRAIL and of the pro-inflammatory cytokines TNFalpha and IL-6 by CpG-activated PDC. These effects were associated with the inhibition of IFN Regulatory Factor (IRF)-7 nuclear translocation. Furthermore, TSA was also effective in inhibiting the production of IFNalpha by PDC cultured in vitro in the presence of serum obtained from SLE patients. This study describes a new level of regulation of immune responses by histone deacetylase inhibitors and defines the molecular basis for new strategies to be exploited in the treatment of autoimmune diseases.
Salvi
Valentina
V
Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy.
Bosisio
Daniela
D
Mitola
Stefania
S
Andreoli
Laura
L
Tincani
Angela
A
Sozzani
Silvano
S
D021581:Active Transport, Cell Nucleus; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism*; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000378:metabolism
C408982:CPG-oligonucleotide; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D009838:Oligodeoxyribonucleotides; C012589:trichostatin A