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Molecular Medicine

, Volume 17, Issue 5–6, pp 404–416 | Cite as

HDAC Inhibition and Graft Versus Host Disease

  • Sung Choi
  • Pavan Reddy
Review Article

Abstract

Histone deacetylase (HDAC) inhibitors are currently used clinically as anticancer drugs. Recent data have demonstrated that some of these drugs have potent antiinflammatory or immunomodulatory effects at noncytotoxic doses. The immunomodulatory effects have shown potential for therapeutic benefit after allogeneic bone marrow transplantation in several experimental models of graft versus host disease (GVHD). These effects, at least in part, result from the ability of HDAC inhibitors (HDACi) to suppress the function of host antigen presenting cells such as dendritic cells (DC). HDACi reduce the dendritic cell (DC) responses, in part, by enhancing the expression of indoleamine 2,3-dioxygenase (IDO) in a signal transducer and activator of transcription-3 (STAT-3) dependent manner. They also alter the function of other immune cells such as T regulatory cells and natural killer (NK) cells, which also play important roles in the biology of GVHD. Based on these observations, a clinical trial has been launched to evaluate the impact of HDAC inhibitors on clinical GVHD. The experimental, mechanistic studies along with the brief preliminary observations from the ongoing clinical trial are discussed in this review.

Notes

Acknowledgment

Supported by NIH grants: AI075284, HL090775 and CA143379 to PR.

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  1. 1.Department of PediatricsUniversity of Michigan Comprehensive Cancer CenterAnn ArborUSA
  2. 2.Department of Internal Medicine, Division of Hematology and Oncology Blood and Marrow Transplantation ProgramUniversity of Michigan Comprehensive Cancer Center, 3312 CCGCAnn ArborUSA

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