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.