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http://dx.doi.org/10.5483/BMBRep.2021.54.2.254

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)
Publication Information
BMB Reports / v.54, no.2, 2021 , pp. 142-147 More about this Journal
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
Atopic dermatitis; Id2/E2A interaction; IgE; Phosphodiester CpG-ODN; TGF-${\beta}$; Smad7;
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