title: Targeting deacetylases to improve outcomes after allogeneic bone marrow transplantation.
abstract: Graft-versus-host disease (GVHD) is the major complication of allogeneic bone marrow transplantation (BMT). GVHD is a complex immunologically mediated biological process. Recent data have shown that histone deacetylase inhibitors (HDACis) have potent anti-inflammatory effects. We have been studying the role of acetylation through inhibition of histone deacetylases (HDACs) in modulating immunity, specifically, GVHD. HDAC inhibition regulates GVHD, at least in part, through suppression of the function of host antigen presenting cells such as dendritic cells (DCs). HDACis reduce DC responses by enhancing the expression of indoleamine 2,3 dioxygenase (IDO) in a STAT-3-dependent manner. They also alter the function of other immune cells such as T regulatory cells and NK cells, which also play important roles in the biology of GVHD. Based on these observations, a clinical trial has been launched to evaluate its impact on clinical GVHD. The clinical features, biology of GVHD, the experimental studies with HDACis, and preliminary observations from humans are discussed.
authors.affiliation: Division of Nephrology, C3121 MCN, Vanderbilt University School of Medicine and Nashville Veterans Affairs Hospital Nashville, TN 37232, USA. ray.harris@vanderbilt.edu
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
mesh_terms: D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006086:Graft vs Host Disease / Q000503:physiopathology / Q000517:prevention & control*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology
chemical_list: D056572:Histone Deacetylase Inhibitors; D007166:Immunosuppressive Agents; D006655:Histone Deacetylases