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Epigenetic enzymes are the therapeutic targets for CD4+CD25+/highFoxp3+ regulatory T cells

  • Jahaira Lopez-Pastrana
    Affiliations
    Centers for Metabolic Disease Research and Cardiovascular Research, Temple University School of Medicine, Philadelphia, Penn
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  • Ying Shao
    Affiliations
    Centers for Metabolic Disease Research and Cardiovascular Research, Temple University School of Medicine, Philadelphia, Penn
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  • Valeria Chernaya
    Affiliations
    Centers for Metabolic Disease Research and Cardiovascular Research, Temple University School of Medicine, Philadelphia, Penn
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  • Hong Wang
    Affiliations
    Centers for Metabolic Disease Research and Cardiovascular Research, Temple University School of Medicine, Philadelphia, Penn
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  • Xiao-Feng Yang
    Correspondence
    Reprint requests: Xiao-Feng Yang, Centers for Metabolic Disease Research and Cardiovascular Research, Temple University School of Medicine, MERB 1059, 3500 North Broad Street, Philadelphia, PA 19140
    Affiliations
    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
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Published:August 14, 2014DOI:https://doi.org/10.1016/j.trsl.2014.08.001
      CD4+CD25+/highFoxp3+ 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.

      Abbreviations:

      CGIs (CpG islands), DNMTs (DNA methyltransferases), H2Bub1 (histone H2B ubiquitylation), H3S10 (serine 10 of H3), HAT (histone acetyl transferase), HDACi (histone deacetylase inhibitors), HDACs (histone deacetylases), LAP (latency associated peptide), Mbd (methyl-binding domain), ncRNAs (non-coding RNAs), TIP-60 (TAT interactive protein), Tr1 (T regulatory cell type 1), TSA (trichostatin), TSDR (Treg-specific-demethylated region)
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