HDAC inhibitor therapy in autoimmunity and transplantation

Abstract

Pharmacological inhibitors of histone/protein deacetylases (HDACi) have considerable therapeutic potential as anti-inflammatory and immunosuppressive drugs. The utility of HDACi as anti-inflammatory agents is dependent upon their proving safe and effective in experimental models. Current pan-HDACi compounds are ill-suited to this role, given the broad distribution of target HDACs and their complex and multifaceted mechanisms of action. By contrast, the development of isoform-selective HDACi may provide important new tools for treatment in autoimmunity and transplantation. This review discusses which HDACs are worthwhile targets in inflammation, and the progress made towards their therapeutic inhibition, including the use of HDAC subclass and isoform-selective HDACi to promote the functions of Foxp3+ T-regulatory cells.