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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Entinostat, a histone deacetylase inhibitor, increases the population of IL-10+ regulatory B cells to suppress contact hypersensitivity

  • Min, Keun Young (Department of Immunology, School of Medicine, Konkuk University) ;
  • Lee, Min Bum (Department of Immunology, School of Medicine, Konkuk University) ;
  • Hong, Seong Hwi (Department of Biochemistry, School of Medicine, Konkuk University) ;
  • Lee, Dajeong (Department of Immunology, School of Medicine, Konkuk University) ;
  • Jo, Min Geun (Department of Immunology, School of Medicine, Konkuk University) ;
  • Lee, Ji Eon (Department of Immunology, School of Medicine, Konkuk University) ;
  • Choi, Min Yeong (Department of Immunology, School of Medicine, Konkuk University) ;
  • You, Jueng Soo (Department of Biochemistry, School of Medicine, Konkuk University) ;
  • Kim, Young Mi (Department of Preventive Pharmacy, College of Pharmacy, Duksung Women's University) ;
  • Park, Yeong Min (Department of Immunology, School of Medicine, Konkuk University) ;
  • Kim, Hyuk Soon (Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, Dong-A University) ;
  • Choi, Wahn Soo (Department of Immunology, School of Medicine, Konkuk University)
  • Received : 2021.07.13
  • Accepted : 2021.08.29
  • Published : 2021.10.31
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Abstract

IL-10+ regulatory B (Breg) cells play a vital role in regulating the immune responses in experimental autoimmune encephalomyelitis, colitis, and contact hypersensitivity (CHS). Several stimulants such as lipopolysaccharide (LPS), CD40 ligand, and IL-21 spur the activation and maturation of IL-10+ Breg cells, while the epigenetic mechanism for the IL-10 expression remains largely unknown. It is well accepted that the histone acetylation/deacetylation is an important mechanism that regulates the expression of IL-10. We found that entinostat, an HDAC inhibitor, stimulated the induction of IL-10+ Breg cells by LPS in vitro and the formation of IL-10+ Breg cells to suppress CHS in vivo. We further demonstrated that entinostat inhibited HDAC1 from binding to the proximal region of the IL-10 expression promoter in splenic B cells, followed by an increase in the binding of NF-κB p65, eventually enhancing the expression of IL-10 in Breg cells.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2021R1A2B5B03002157, NRF-2020R1C1C1003676, and NRF-2016R1A5A2012284).

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