Immunomodulatory effects of deacetylase inhibitors: therapeutic targeting of FOXP3+ regulatory T cells.
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.
Division of Transplant Immunology, Children's Hospital of Philadelphia, Philadelphia 19104, USA.
Liqing
L
Wang
Edwin F
EF
de Zoeten
Mark I
MI
Greene
Wayne W
WW
Hancock
D000818:Animals; D016503:Drug Delivery Systems; D015195:Drug Design; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D016377:Organ Transplantation / Q000379:methods; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000201:enzymology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D056572:Histone Deacetylase Inhibitors; D007155:Immunologic Factors