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

Fengdong Cheng, Maritza Lienlaf, Patricio Perez-Villarroel, Hong Wei Wang, Calvin Lee, Karrune Woan, David Woods, Tessa Knox, Joel Bergman, Javier Pinilla-Ibarz, Alan Kozikowski, Edward Seto, Eduardo M. Sotomayor, Alejandro Villagra

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)44-53
Number of pages10
JournalMolecular Immunology
Volume60
Issue number1
DOIs
StatePublished - Jul 2014

Keywords

  • Antigen presenting cells
  • HDAC11
  • HDAC6
  • IL-10
  • Tolerance

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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    Cheng, F., Lienlaf, M., Perez-Villarroel, P., Wang, H. W., Lee, C., Woan, K., Woods, D., Knox, T., Bergman, J., Pinilla-Ibarz, J., Kozikowski, A., Seto, E., Sotomayor, E. M., & Villagra, A. (2014). Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells. Molecular Immunology, 60(1), 44-53. https://doi.org/10.1016/j.molimm.2014.02.019