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.

Trichostatin A blocks type I interferon production by activated plasmacytoid dendritic cells / V., Salvi; Bosisio, Daniela; Mitola, Stefania Maria Filomena; Andreoli, Laura; Tincani, Angela; Sozzani, Silvano. - In: IMMUNOBIOLOGY. - ISSN 0171-2985. - 215:(2010), pp. 756-761. [10.1016/j.imbio.2010.05.023]

Trichostatin A blocks type I interferon production by activated plasmacytoid dendritic cells

SOZZANI, Silvano
2010

Abstract

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.
2010
01 Pubblicazione su rivista::01a Articolo in rivista
Trichostatin A blocks type I interferon production by activated plasmacytoid dendritic cells / V., Salvi; Bosisio, Daniela; Mitola, Stefania Maria Filomena; Andreoli, Laura; Tincani, Angela; Sozzani, Silvano. - In: IMMUNOBIOLOGY. - ISSN 0171-2985. - 215:(2010), pp. 756-761. [10.1016/j.imbio.2010.05.023]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1371420
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