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

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

Author information

1
Division of Transplant Immunology, Children's Hospital of Philadelphia, Philadelphia 19104, USA.

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.

PMID:
19855427
PMCID:
PMC2884987
DOI:
10.1038/nrd3031
[Indexed for MEDLINE]
Free PMC Article

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