Differences of Circulating CD25hi Bregs and Their Correlations with CD4 Effector and Regulatory T Cells in Autoantibody-Positive T1D Compared with Age-Matched Healthy Individuals.

Jie Zhang,Tao Yang,Yuyue Zhang,Heng Chen,Yu Qian,Qi Fu,Xinyu Xu,Kuanfeng Xu,Yunqiang He,Hui Lv,Payam Behzadi

doi:10.1155/2022/2269237

Abstract

Circulating CD25hi B cells, a subset of regulatory B cells in humans, are closely related to inflammation and autoimmune diseases. This study is aimed at investigating the alternation of CD25hi Bregs and their correlation with CD4 effector and regulatory T cells in T1D individuals. We included 68 autoantibody-positive T1D and 68 age-matched healthy individuals with peripheral blood mononuclear cells (PBMCs) and assessed them with CD25hi Bregs and CD4 effector or regulatory T cells by flow cytometry. Here, we demonstrate that the frequency of CD25hi Bregs was significantly decreased in T1D subjects (P = 0.0016), but they were not affected by disease status (age at T1D diagnosis or duration) or T1D risk loci (rs2104286 or rs12251307) in IL2RA (all P > 0.05). Moreover, higher IgD (P = 0.043) and lower CD27 (P = 0.0003) expression was observed in CD25hi Bregs of T1D individuals, but not the expression of IgM, CD24, or CD38 (all P > 0.05). Although there was no correlation between CD25hi Bregs and CD4 effector T cell subsets in either T1D or healthy individuals (all P > 0.05), we found a positive correlation between CD25hi Bregs and CD4 Tregs in healthy controls (Sp. r = 0.3544, P = 0.0249), which disappeared in T1D subjects (Sp. r = 0.137, P = 0.401). In conclusion, our results suggest that decreased CD25hi Bregs and alternation of their phenotypes are features of T1D regardless of disease duration and T1D genetic risk loci, and an impaired balance between CD25hi Bregs and CD4 Tregs might contribute to the pathogenesis of T1D.

Highlights

Type 1 diabetes (T1D) is an organ-specific autoimmune disease mediated by T cells against pancreatic β cells
CD25hi Bregs Do Not Correlate with Age at T1D Diagnosis, T1D Duration, or T1D Risk Loci in the IL2RA Region
IgM, IgD, CD24, and CD38 expression does not correlate with age at the time of donation, our results show that the expression of CD27 in CD25hi Bregs has a positive correlation with age at drawn in healthy donors (Figures S3A–E)

Summary

Introduction

Type 1 diabetes (T1D) is an organ-specific autoimmune disease mediated by T cells against pancreatic β cells. B cells play an essential role in the autoimmune destruction of β cells [4, 5], which mainly participate in the T cell immune response by producing autoantibodies, presenting antigens, secreting cytokines, and providing costimulatory signals [6,7,8]. Bregs can be divided into different regulatory subsets, including B10 cells, plasmablasts, Br1 cells, and immature B cells in humans [9]. They are involved in the immune process by producing interleukin- (IL-) 10, IL-35, and transforming growth factor-β (TGF-β), inhibiting the proliferation of CD4 effector T cells, and enhancing the expression of FOXP3 and k k

Objectives

Methods

Conclusion