Histone/protein deacetylases control Foxp3 expression and the heat shock response of T-regulatory cells

Curr Opin Immunol. 2011 Oct;23(5):670-8. doi: 10.1016/j.coi.2011.07.002. Epub 2011 Jul 26.


Lysine ɛ-acetylation is a post-translational modification that alters the biochemical properties of many proteins. The reaction is catalyzed by histone/protein acetyltransferases (HATs), and is reversed by histone/protein deacetylases (HDACs). As a result, HATs and HDACs constitute an important, though little recognized, set of proteins that control the functions of T-regulatory (Treg) cells. Targeting certain HDACs, especially HDAC6, HDAC9, and Sirtuin-1 (Sirt1), can augment Treg suppressive potency by several distinct and potentially additive mechanisms. These involve promoting Forkhead box p3 (Foxp3) gene expression and preserving Foxp3 lysine ɛ-acetylation, which infers resistance to ubiquitination and proteasomal degradation, and increases DNA binding. Moreover, depleting certain HDAC can enhance the heat shock response, which increases the tenacity of Treg to survive under stress, and helps preserve a suppressive phenotype. As a result, HDAC inhibitor therapy can be used to enhance Treg functions in vivo and have beneficial effects on allograft survival and autoimmune diseases.

Publication types

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

MeSH terms

  • Acetylation
  • Adaptive Immunity*
  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology*
  • Gene Expression Regulation / immunology
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Heat-Shock Response / immunology
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / immunology*
  • Histone Acetyltransferases / metabolism
  • Histone Deacetylase Inhibitors / administration & dosage
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / immunology*
  • Histone Deacetylases / metabolism
  • Humans
  • Mice
  • Organ Transplantation*
  • Protein Processing, Post-Translational / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • Ubiquitination


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Histone Deacetylase Inhibitors
  • Histone Acetyltransferases
  • Histone Deacetylases