title: Rationale for HDAC inhibitor therapy in autoimmunity and transplantation.
abstract: While there are currently more than 70 ongoing clinical trials of inhibitors of so-called classical HDACs (HDACi) as anticancer therapies, given their potency as antiproliferative and angiostatic agents, HDACi also 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 not well suited to this role, given the broad distribution of target HDACs and their complex and multifaceted mechanisms of action. In contrast, the development of isoform-selective HDACi may provide important new tools for therapy in autoimmunity and transplantation. This chapter discusses which HDACs are worthwhile targets in inflammation and progress toward their therapeutic inhibition, including the use of HDAC subclass and isoform-selective HDACi to promote the functions of Foxp3+ T regulatory cells.
authors: Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, 916B Abramson Research Center, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4318, USA. whancock@mail.med.upenn.edu
authors: Wayne W
authors: WW
authors: Hancock
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007527:Isoenzymes; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D023001:Transplantation Tolerance / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D056572:Histone Deacetylase Inhibitors; D007166:Immunosuppressive Agents; D007527:Isoenzymes; D006655:Histone Deacetylases