Anti-CD20 therapy ameliorates β cell function and rebalances Th17/Treg cells in NOD mice
- 24 January 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in Endocrine
- Vol. 76 (1), 44-52
- https://doi.org/10.1007/s12020-021-02965-x
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.Funding Information
- Natural Science Foundation of Hubei Province (2019CFB102)
- Hubei Provincial Population and Family Planning Commission (WJ2015MB098)
This publication has 40 references indexed in Scilit:
- Type 1 diabetes: translating mechanistic observations into effective clinical outcomesNature Reviews Immunology, 2013
- The Serum IL-6 Profile and Treg/Th17 Peripheral Cell Populations in Patients with Type 1 DiabetesMediators of Inflammation, 2013
- Expansion of Th17 Cells and Functional Defects in T Regulatory Cells Are Key Features of the Pancreatic Lymph Nodes in Patients With Type 1 DiabetesDiabetes, 2011
- Change you can B(cell)eive in: recent progress confirms a critical role for B cells in type 1 diabetesCurrent Opinion in Endocrinology, Diabetes and Obesity, 2009
- Inhibition of Th17 Cells Regulates Autoimmune Diabetes in NOD MiceDiabetes, 2009
- Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in miceJCI Insight, 2007
- IL‐23 leads to diabetes induction after subdiabetogenic treatment with multiple low doses of streptozotocinEuropean Journal of Immunology, 2005
- THE NOD MOUSE: A Model of Immune DysregulationAnnual Review of Immunology, 2005
- IL-23 drives a pathogenic T cell population that induces autoimmune inflammationThe Journal of Experimental Medicine, 2005
- CpG oligodeoxynucleotides accelerate reovirus type 2-triggered insulitis in DBA/1 suckling miceInternational Journal of Experimental Pathology, 2003