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

2009; Nature Portfolio; Volume: 8; Issue: 12 Linguagem: Inglês

10.1038/nrd3031

1474-1784

Liqing Wang, Edwin F. de Zoeten, Mark I. Greene, Wayne W. Hancock,

Immune Cell Function and Interaction

Many inhibitors of histone deacetylases (HDACs) are in trials in patients with cancer, but a subset of HDAC inhibitors also have anti-inflammatory or immunosuppressive effects that may be of therapeutic benefit in autoimmune diseases or post-transplantation. Hancock and colleagues describe these effects, highlighting the importance of the ability of some HDAC inhibitors to enhance the production and suppressive functions of FOXP3+regulatory T cells, and discuss the potential to develop class- or subclass-specific HDAC inhibitors as novel immunotherapies. 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.