title: Epigenetic enzymes are the therapeutic targets for CD4(+)CD25(+/high)Foxp3(+) regulatory T cells.
abstract: 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.
authors.affiliation: Centers for Metabolic Disease Research and Cardiovascular Research, Temple University School of Medicine, Philadelphia, Penn.
authors.forename: Jahaira
authors.initials: J
authors.lastname: Lopez-Pastrana
authors.affiliation: Centers for Metabolic Disease Research and Cardiovascular Research, Temple University School of Medicine, Philadelphia, Penn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Centers for Metabolic Disease Research and Cardiovascular Research, Temple University School of Medicine, Philadelphia, Penn.
authors.forename: Valeria
authors.initials: V
authors.lastname: Chernaya
authors.affiliation: Centers for Metabolic Disease Research and Cardiovascular Research, Temple University School of Medicine, Philadelphia, Penn.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Centers for Metabolic Disease Research and Cardiovascular Research, Temple University School of Medicine, Philadelphia, Penn; Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Penn. Electronic address: jahapastrana@gmail.com.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D061166:Peripheral Tolerance / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D057170:Translational Research, Biomedical
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D022661:RNA, Untranslated; D006655:Histone Deacetylases