Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells

Mol Immunol. 2014 Jul;60(1):44-53. doi: 10.1016/j.molimm.2014.02.019. Epub 2014 Apr 18.


The anti-inflammatory cytokine IL-10 is a key modulator of immune responses. A better understanding of the regulation of this cytokine offers the possibility of tipping the balance of the immune response toward either tolerance, or enhanced immune responses. Histone deacetylases (HDACs) have been widely described as negative regulators of transcriptional regulation, and in this context, the primarily nuclear protein HDAC11 was shown to repress il-10 gene transcriptional activity in antigen-presenting cells (APCs). Here we report that another HDAC, HDAC6, primarily a cytoplasmic protein, associates with HDAC11 and modulates the expression of IL-10 as a transcriptional activator. To our knowledge, this is the first demonstration of two different HDACs being recruited to the same gene promoter to dictate divergent transcriptional responses. This dynamic interaction results in dynamic changes in the expression of IL-10 and might help to explain the intrinsic plasticity of the APC to determine T-cell activation versus T-cell tolerance.

Keywords: Antigen presenting cells; HDAC11; HDAC6; IL-10; Tolerance.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Cell Line
  • Gene Expression Regulation
  • Histone Deacetylase 6
  • Histone Deacetylases / genetics
  • Histone Deacetylases / immunology*
  • Immune Tolerance / genetics
  • Immune Tolerance / immunology
  • Interleukin-10 / genetics*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Small Interfering
  • T-Lymphocytes / immunology
  • Transcription, Genetic
  • Transcriptional Activation / immunology


  • IL10 protein, mouse
  • RNA, Small Interfering
  • Interleukin-10
  • Hdac11 protein, mouse
  • Hdac6 protein, mouse
  • Histone Deacetylase 6
  • Histone Deacetylases