1. Anti-CD20 therapy ameliorates β cell function and rebalances Th17/Treg cells in NOD mice.
- Author
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Chen M, Zhang Q, Wei Y, Wan Q, Xu M, and Chen X
- Subjects
- Animals, Humans, Inflammation metabolism, Interleukin-17, Mice, Mice, Inbred NOD, Th17 Cells, Transforming Growth Factor beta metabolism, Diabetes Mellitus, Type 1, T-Lymphocytes, Regulatory
- 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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2022
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