HDAC inhibitor therapy in autoimmunity and transplantation
- 1Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
- 2Division of Nephrology, Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
- Correspondence to Wayne W Hancock, Division of Transplant Immunology, Pathology and Laboratory Medicine, 916B Abramson Research Center, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4318, USA;
- Received 6 October 2011
- Accepted 14 October 2011
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.
Funding National Institutes of Health. Supported in part by a research grant from the National Institutes of Health to WWH (P01AI073489).
Competing interests None.
Provenance and peer review Commissioned; externally peer reviewed.