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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Treatment with phosphodiester CpG-ODN ameliorates atopic dermatitis by enhancing TGF-β signaling

  • Ham, Won-Kook (Department of Dermatology, College of Medicine, The Catholic University of Korea) ;
  • Lee, Eun-Jung (Department of Dermatology, College of Medicine, The Catholic University of Korea) ;
  • Jeon, Myung Shin (Translational Research Center, Department of Molecular Biomedicine, IRIMS, and College of Medicine, Inha University) ;
  • Kim, Hae-Young (Department of Dermatology, College of Medicine, The Catholic University of Korea) ;
  • Agrahari, Gaurav (Department of Dermatology, College of Medicine, The Catholic University of Korea) ;
  • An, Eun-Joo (Department of Dermatology, College of Medicine, The Catholic University of Korea) ;
  • Bang, Chul Hwan (Department of Dermatology, College of Medicine, The Catholic University of Korea) ;
  • Kim, Doo-Sik (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Kim, Tae-Yoon (Department of Dermatology, College of Medicine, The Catholic University of Korea)
  • Received : 2020.11.13
  • Accepted : 2021.01.04
  • Published : 2021.02.28
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Abstract

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG phosphorothioate (PS CpG-ODN) are known to decrease IgE synthesis in Th2 allergy responses. Nonetheless, the therapeutic role of PS CpG-ODN is limited due to cytotoxicity. Therefore, we developed a phosphodiester (PO) form of CpG-ODN (46O) with reduced toxicity but effective against allergies. In this study, we first compared the toxicity of 46O with CpG-ODNs containing a PS backbone (1826S). We also investigated the therapeutic efficacy and mechanism of 46O injected intravenously in a mouse model of ovalbumin (OVA)-induced atopic dermatitis (AD). To elucidate the mechanism of 46O underlying the inhibition of IgE production, IgE- and TGF-β-associated molecules were evaluated in CD40/IL-4- or LPS/IL-4-stimulated B cells. Our data showed that the treatment with 46O was associated with a lower hematological toxicity compared with 1826S. In addition, injection with 46O reduced erythema, epidermal thickness, and suppressed IgE and IL-4 synthesis in mice with OVA-induced AD. Additionally, 46O induced TGF-β production in LPS/IL-4-stimulated B cells via inhibition of Smad7, which suppressed IgE synthesis via interaction between Id2 and E2A. These findings suggest that enhanced TGF-β signaling is an effective treatment for IgE-mediated allergic conditions, and 46O may be safe and effective for treating allergic diseases such as AD and asthma.

Keywords

References

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