Immunomodulatory effects of deacetylase inhibitors: therapeutic targeting of FOXP3+ regulatory T cells

Nat Rev Drug Discov. 2009 Dec;8(12):969-81. doi: 10.1038/nrd3031. Epub 2009 Oct 26.

Abstract

Classical zinc-dependent histone deacetylases (HDACs) catalyse the removal of acetyl groups from histone tails and also from many non-histone proteins, including the transcription factor FOXP3, a key regulator of the development and function of regulatory T cells. Many HDAC inhibitors are in cancer clinical trials, but a subset of HDAC inhibitors has important anti-inflammatory or immunosuppressive effects that might be of therapeutic benefit in immuno-inflammatory disorders or post-transplantation. At least some of these effects result from the ability of HDAC inhibitors to enhance the production and suppressive functions of FOXP3(+) regulatory T cells. Understanding which HDACs contribute to the regulation of the functions of regulatory T cells may further stimulate the development of new class- or subclass-specific HDAC inhibitors with applications beyond oncology.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems
  • Drug Design
  • Forkhead Transcription Factors / metabolism*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Immunologic Factors / pharmacology*
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Organ Transplantation / methods
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / enzymology

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Histone Deacetylase Inhibitors
  • Immunologic Factors