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Anti-CD20 therapy ameliorates β cell function and rebalances Th17/Treg cells in NOD mice

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Abstract

Purpose

Anti-CD20 therapy delays type 1 diabetes mellitus (T1DM) progression in both nonobese diabetic (NOD) mice and new-onset patients. The mechanism is not completely defined. This study aimed to investigate the effects of anti-CD20 therapy on T helper 17 (Th17) cells and regulatory T cells (Tregs) in NOD mice. The role of B cell depletion in T1DM development was also examined.

Methods

NOD mice were randomly divided into two groups. The mice in the experimental group were treated with an anti-CD20 antibody, while the control mice were treated with an isotype-matched control antibody. After treatment, islet morphology and inflammation, Th17 and Treg cell frequencies in the pancreas and spleen, serum cytokine and anti-glutamic acid decarboxylase (GAD) antibody levels, interleukin (IL)-17A levels in the pancreas and spleen, insulin expression in islet cells and islet β cell function were measured.

Results

Decreased blood glucose and increased insulin secretion were found in the exprimental group compared with the CON group. A lower islet inflammation score was also found in the experimental group. Decreased Th17 cell and IL-17A levels and augmented Treg cell levels were found in the spleen and pancreas after anti-CD20 treatment. The serum levels of B cell activating factor (BAFF), IL-17A, IL-17F, IL-23 and anti-GAD autoantibodies were decreased in the experimental group, while higher serum levels of IL-10 and transforming growth factor (TGF)-β were found.

Conclusion

Anti-CD20 therapy might have some beneficial effects that improve β cell function by relieving islet inflammation through regulation of Th17/Treg cells and the proinflammatory/anti-inflammatory balance.

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Funding

This work was supported by the Hubei Province Natural Science Fund (2019CFB102) and the Health & Family Planning Commission Fund (WJ2015MB098).

Author contributions

XQC participated in the design of the study. MC and QHZ contributed to completion of the experiments. YHW, QQW and XM analyzed the data. MC and XQC wrote the main manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuhan, China

    Min Chen, Qianhui Zhang, Yanhong Wei, Qianqian Wan, Min Xu & Xiaoqi Chen

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  1. Min Chen
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Correspondence to Xiaoqi Chen.

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All procedures in the study involving animals were performed in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH Pub. No. 85–23, revised 1996) and approved by the Institutional Animal Care and Use Committee (IACUC) at the Centre for Animal Experiments, Wuhan University.

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Chen, M., Zhang, Q., Wei, Y. et al. Anti-CD20 therapy ameliorates β cell function and rebalances Th17/Treg cells in NOD mice. Endocrine 76, 44–52 (2022). https://doi.org/10.1007/s12020-021-02965-x

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  • DOI: https://doi.org/10.1007/s12020-021-02965-x

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