HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies

Theranostics. 2017 Feb 23;7(4):1002-1009. doi: 10.7150/thno.17615. eCollection 2017.


The pro-inflammatory cytokine interleukin 17 (IL-17) is critically involved in immunity and inflammation. T-helper 17 and γδ T cells are the predominant sources of IL-17 in the immune system. However, the mechanisms by which the expression of IL-17 is regulated in T cells remain elusive. Here, we demonstrate that loss of histone deacetylase 6 (HDAC6) in mice does not affect the generation of CD4+ or CD8+ T cells, but stimulates the development of IL-17-producing γδ T cells. Our data further show that HDAC6 deficiency increases the production of IL-17 by Vγ4+ γδ T cells in the spleen and lymph nodes. Consistent with these observations, small-molecule inhibition of HDAC6 activity in γδ T cells promotes the expression of IL-17 in vitro. These data thus reveal that HDAC6 represses IL-17 production in T cells, providing novel insights into the role of HDAC6 in the immune system. These findings also have important implications for the clinical investigation of HDAC6-targeted therapies.

Keywords: T cell; development; histone deacetylase 6; interleukin 17; knockout mouse..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Histone Deacetylase 6
  • Histone Deacetylases / metabolism*
  • Interleukin-17 / biosynthesis*
  • Lymph Nodes / immunology
  • Mice
  • Receptors, Antigen, T-Cell, gamma-delta / analysis*
  • Spleen / immunology
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / metabolism*


  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Hdac6 protein, mouse
  • Histone Deacetylase 6
  • Histone Deacetylases