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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen-Presenting Cells / enzymology
  • Antigen-Presenting Cells / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Line
  • Down-Regulation
  • Gene Expression Regulation*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Immune Tolerance / genetics*
  • Interleukin-10 / genetics*
  • Lymphocyte Activation / genetics
  • Male
  • Mice
  • Mice, Inbred BALB C


  • Interleukin-10
  • HDAC11 protein, human
  • Hdac11 protein, mouse
  • Histone Deacetylases