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

L Wang, EF De Zoeten, MI Greene… - Nature reviews Drug …, 2009 - nature.com
Nature reviews Drug discovery, 2009nature.com
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 …
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.
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