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Nat Immunol. 2009 Jan;10(1):92-100. doi: 10.1038/ni.1673. Epub 2008 Nov 16.

The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance.

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  • 1Division of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.

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  • Nat Immunol. 2009 Jun;10(6):665.


Antigen-presenting cells (APCs) induce T cell activation as well as T cell tolerance. The molecular basis of the regulation of this critical 'decision' is not well understood. Here we show that HDAC11, a member of the HDAC histone deacetylase family with no prior defined physiological function, negatively regulated expression of the gene encoding interleukin 10 (IL-10) in APCs. Overexpression of HDAC11 inhibited IL-10 expression and induced inflammatory APCs that were able to prime naive T cells and restore the responsiveness of tolerant CD4+ T cells. Conversely, disruption of HDAC11 in APCs led to upregulation of expression of the gene encoding IL-10 and impairment of antigen-specific T cell responses. Thus, HDAC11 represents a molecular target that influences immune activation versus immune tolerance, a critical 'decision' with substantial implications in autoimmunity, transplantation and cancer immunotherapy.

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