Histone deacetylase inhibitors and transplantation

• Published in: Current Opinion in Immunology 2007-10, Vol.19 (5), p.589-595
• Main Authors: Tao, Ran, de Zoeten, Edwin F, Ozkaynak, Engin, Wang, Liqing, Li, Bin, Greene, Mark I, Wells, Andrew D, Hancock, Wayne W
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Epigenesis, Genetic; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Histone Deacetylase Inhibitors; Histone Deacetylases - metabolism; Humans; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Transplantation Immunology
• ISSN: 0952-7915; 1879-0372; 1365-2567
• DOI: 10.1016/j.coi.2007.07.015

Simply detecting the presence or absence of Foxp3, a transcription factor characteristic of naturally occurring CD4+ CD25+ regulatory T cells (Tregs), now appears of minimal value in predicting the outcome of immunologic responses, since dividing human CD4+ effector T cells can induce Foxp3 without attaining repressive functions, and additional molecular interactions, as well epigenetic events, affect Foxp3-dependent Treg functions in humans and mice. Experimentally, in vivo and in vitro studies show histone deacetylase inhibitors (HDACi) can enhance the numbers and suppressive function of regulatory T cells (Tregs) by promoting Foxp3+ cell production, enhancing chromatin remodeling within Tregs, and inducing acetylation of Foxp3 protein itself. Human studies consistent with a role for HDACi in controlling Fox3-dependent Treg functions are also available. We review these molecular interactions and how they may be exploited therapeutically to enhance Treg-dependent functions, including post-transplantation.