Epigenetic enzymes are the therapeutic targets for CD4+ CD25+/high Foxp3+ regulatory T cells

• Published in: Translational research : the journal of laboratory and clinical medicine Vol. 165; no. 1; pp. 221 - 240
• Main Authors: Lopez-Pastrana, Jahaira, Shao, Ying, Chernaya, Valeria, Wang, Hong, Yang, Xiao-Feng
• Format: Journal Article
• Language: English
• Published: 2015
• Subjects: Internal Medicine; DNMTs; HDACs; DNA methyltransferases; TIP-60; serine 10 of H3; ncRNAs; Mbd; T regulatory cell type 1; trichostatin; H2Bub1; Tr1; histone deacetylases; HDACi; CpG islands; histone deacetylase inhibitors; TSA; H3S10; TSDR; TAT interactive protein; histone acetyl transferase; Treg-specific-demethylated region; methyl-binding domain; CGIs; histone H2B ubiquitylation; latency associated peptide; non-coding RNAs; HAT; LAP
• ISSN: 1931-5244
• DOI: 10.1016/j.trsl.2014.08.001

CD4+ CD25+/high Foxp3+ regulatory T (Treg) cells are a subset of CD4+ T cells that play an essential role in maintaining peripheral immune tolerance. Several transcriptional cofactors have been recently identified, which form complexes with transcription factor Foxp3 of Treg cells and contribute in the suppressive function of Treg cells. However, Foxp3 is still defined as a “master” (multiple pathway) regulator gene that controls the development and stability of Treg cells. Because of its importance, the regulatory mechanisms underlying Foxp3 expression have been a focus of intensive investigation. Recent progress suggests that the epigenetic mechanisms responsible for regulating the Foxp3 gene expression are key components of suppressive activity of Treg cells. This review not only discusses the basic concepts of biology and epigenetic modifications of Treg cells, but also analyzes the translational clinical aspect of epigenetic modifications of Treg cells, focusing on several ongoing clinical trials and the Food and Drugs administration (FDA) approved epigenetic-based drugs. The new progress in identifying epigenetic enzymes functional in Treg cells is a new target for the development of novel therapeutic approaches for autoimmune and inflammatory diseases, graft-vs-host disease and cancers.