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

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.

• Authors: Min Chen, Qianhui Zhang, Yanhong Wei, Qianqian Wan, Min Xu, Xiaoqi Chen
• Journal: Endocrine (Endocrine) Vol. 76 Issue 1 Pg. 44-52 (04 2022) ISSN: 1559-0100 [Electronic] United States
• PMID: 35067899 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Interleukin-17
• Transforming Growth Factor beta

Topics

• Animals
• Diabetes Mellitus, Type 1
• Humans
• Inflammation (metabolism)
• Interleukin-17
• Mice
• Mice, Inbred NOD
• T-Lymphocytes, Regulatory
• Th17 Cells
• Transforming Growth Factor beta (metabolism)