title: Histone deacetylase inhibitors and transplantation.
abstract: 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.
authors.affiliation: Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104-4318, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.forename: Edwin F
authors.initials: EF
authors.lastname: de Zoeten
authors.forename: Engin
authors.initials: E
authors.lastname: Ozkaynak
authors.forename: Liqing
authors.initials: L
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Mark I
authors.initials: MI
authors.lastname: Greene
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Wells
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Hancock
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014181:Transplantation Immunology
chemical_list: D051858:Forkhead Transcription Factors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases