Clinical and experimental studies show that inhibition of histone/protein deacetylases (HDAC) can have important anti-neoplastic effects through cytotoxic and pro-apoptotic mechanisms. There are also increasing data from non-oncologic settings that HDAC inhibitors (HDACi) can exhibit useful anti-inflammatory effects in vitro and in vivo, unrelated to cytotoxicity or apoptosis. These effects can be cell, tissue or context-dependent, and can involve modulation of specific inflammatory signaling pathways, as well as epigenetic mechanisms. We review recent advances in the understanding of how HDACi alter immune and inflammatory processes, with a particular focus on the effects of HDACi on T cell biology, including the activation and functions of conventional T cells and the unique T cell subset, comprised of Foxp3+ T-regulatory cells. While studies are still needed to tease out details of the various biological roles of individual HDAC isoforms and their corresponding selective inhibitors, the anti-inflammatory effects of HDACi are already promising and may lead to new therapeutic avenues in transplantation and autoimmune diseases.
- Submitted October 5, 2011.
- Accepted January 6, 2012.
- Copyright © 2005 American Society of Hematology