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A20 Restores Impaired Intestinal Permeability and Inhibits Th2 Response in Mice with Colitis

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Abstract

Background/Aims

The etiology of inflammatory bowel disease is multifactorial and still obscure. The protective role of ubiquitin E3 ligase A20 (A20) in colitis needs to be further elucidated. This study aimed to investigate whether A20 exogenous administration restored impaired intestinal permeability and inhibited T helper (Th)2 response in mice with colitis.

Methods

The effect of A20 overexpression in colonic mucosa on epithelial barrier function and T cell differentiation was evaluated in mice with dextran sulfate sodium (DSS)-induced chronic colitis.

Results

A20 rectal treatment alleviated DSS-induced chronic colitis and restored impaired intestinal permeability. Oral challenge with 2% DSS elicited a Th2-type response in mice with colitis, and A20 rectal treatment inhibited CD4+ interleukin (IL)-4+ T cell differentiation and proliferation. In addition, the RNA expressions of Th2-related costimulatory molecular T-cell immunoglobulin and mucin domain (TIM)-1 and IL-4 were suppressed, while thrombospondin (TSP)-1 and interferon (IFN)-γ expressions were upregulated, after A20 rectal administration.

Conclusion

A20 rectal treatment restores impaired intestinal permeability and inhibits activated Th2 cell response in mice with colitis.

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Acknowledgments

This work was supported by the Natural Science Foundation of China (81571790, 81773978) and grants from the Innovation of Science and Technology Commission of Shenzhen Municipality (JCYJ20160429091935720, JCYJ20170302165727389, and ZDSYS201506050935272). The funding sources had no role in study design, implementation, data collection, analysis, or interpretation, or in the preparation, review, or approval of the manuscript.

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Authors and Affiliations

  1. Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, 457000, China

    Donghui Chen

  2. Longgang ENT Hospital, Institute of ENT, Shenzhen Key Laboratory of ENT, No. 3004, Longgang Avenue, Longgang District, Shenzhen, 518172, China

    Li Ma, Tianyong Hu, Jiangqi Liu, Baohui Chen & Zhiqiang Liu

  3. State Key Laboratory of Respiratory Disease for Allergy, Shenzhen University School of Medicine, Shenzhen University, Shenzhen, 518061, China

    Pingchang Yang

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  1. Donghui Chen
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  2. Li Ma
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  3. Tianyong Hu
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  4. Jiangqi Liu
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Contributions

Guarantors of the article: TH and ZL; ZL, DC, and PY contributed to the study design and the grant; DC, LM, and TH performed the experiments; JL and BC analyzed the data; ZL wrote the manuscript.

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Correspondence to Zhiqiang Liu.

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Chen, D., Ma, L., Hu, T. et al. A20 Restores Impaired Intestinal Permeability and Inhibits Th2 Response in Mice with Colitis. Dig Dis Sci 65, 1340–1347 (2020). https://doi.org/10.1007/s10620-019-05860-8

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  • DOI: https://doi.org/10.1007/s10620-019-05860-8

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