Histone deacetylases inhibitor Trichostatin A ameliorates DNFB-induced allergic contact dermatitis and reduces epidermal Langerhans cells in mice

J Dermatol Sci. 2012 Nov;68(2):99-107. doi: 10.1016/j.jdermsci.2012.09.001. Epub 2012 Sep 7.


Background: Histone deacetylases (HDACs) influence chromatin organization, representing a key epigenetic regulatory mechanism in cells. Trichostatin A (TSA), a potent HDAC inhibitor, has anti-tumor and anti-inflammatory effects. Allergic contact dermatitis (ACD) is a T-cell-mediated inflammatory reaction in skin and is regulated by epidermal Langerhans cells (LCs).

Objective: The aim of this study was to investigate if TSA treatment prevents 2,4-dinitrofluorobenzene (DNFB)-induced ACD in mice and regulates epidermal LCs and other immune cells during ACD development.

Methods: ACD was induced by sensitizing and challenging with DNFB topically. Mice were treated intraperitoneally with TSA or vehicle DMSO as a control every other day before and during induction of ACD. The ear swelling response was measured and skin biopsies from sensitized skin areas were obtained for histology. Epidermal cells, thymus, spleen and skin draining lymph nodes were collected for immune staining.

Results: TSA treatment ameliorated skin lesion severity of DNFB-induced ACD. The percentages of epidermal LCs and splenic DCs as well as LC maturation were significantly reduced in TSA-treated mice. However, TSA treatment did not significantly affect the homeostasis of conventional CD4(+) and CD8(+) T cells, Foxp3(+)CD4(+) regulatory T cells, iNKT cells, and γδ T cells in thymus, spleen and draining lymph nodes (dLNs). Furthermore, there were no significant differences in IL-4 and IFN-γ-producing T cells and iNKT cells between TSA- and DMSO-treated mice.

Conclusion: Our findings suggest that TSA may ameliorate ACD through the regulation of epidermal LCs and HDACs could serve as potential therapeutic targets for ACD and other LCs-related skin diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dermatitis, Allergic Contact / drug therapy*
  • Dinitrofluorobenzene / pharmacology
  • Forkhead Transcription Factors / analysis
  • Histone Deacetylase Inhibitors / pharmacology*
  • Hydroxamic Acids / pharmacology*
  • Langerhans Cells / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell, gamma-delta / analysis
  • T-Lymphocytes / drug effects


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Receptors, Antigen, T-Cell, gamma-delta
  • trichostatin A
  • Dinitrofluorobenzene