Histone deacetylase inhibitors and transplantation.
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.
Tao
Ran
R
Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104-4318, USA.
de Zoeten
Edwin F
EF
Ozkaynak
Engin
E
Wang
Liqing
L
Li
Bin
B
Greene
Mark I
MI
Wells
Andrew D
AD
Hancock
Wayne W
WW
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
D051858:Forkhead Transcription Factors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases