Blood Journal
Leading the way in experimental and clinical research in hematology

Histone/protein deacetylases and T-cell immune responses

  1. Tatiana Akimova1,
  2. Ulf H. Beier2,3,
  3. Yujie Liu1,
  4. Liqing Wang1, and
  5. Wayne W. Hancock1,3
  1. 1Division of Transplant Immunology, Department of Pathology and Laboratory Medicine and
  2. 2Division of Nephrology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; and
  3. 3University of Pennsylvania School of Medicine, Philadelphia, PA

Abstract

Clinical and experimental studies show that inhibition of histone/protein deacetylases (HDAC) can have important anti-neoplastic effects through cytotoxic and proapoptotic mechanisms. There are also increasing data from nononcologic settings that HDAC inhibitors (HDACi) can exhibit useful anti-inflammatory effects in vitro and in vivo, unrelated to cytotoxicity or apoptosis. These effects can be cell-, tissue-, or context-dependent and can involve modulation of specific inflammatory signaling pathways as well as epigenetic mechanisms. We review recent advances in the understanding of how HDACi alter immune and inflammatory processes, with a particular focus on the effects of HDACi on T-cell biology, including the activation and functions of conventional T cells and the unique T-cell subset, composed of Foxp3+ T-regulatory cells. Although studies are still needed to tease out details of the various biologic roles of individual HDAC isoforms and their corresponding selective inhibitors, the anti-inflammatory effects of HDACi are already promising and may lead to new therapeutic avenues in transplantation and autoimmune diseases.

  • Submitted October 4, 2011.
  • Accepted January 6, 2012.
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