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Abstract：
Type 1 diabetes (T1D) is an autoimmune disease with a complex aetiology. B cells play an important role in the pathogenesis of T1D. Regulatory B cells (Bregs) are a subset of B cells that produce and secrete the inhibitory factor interleukin-10 (IL-10), thereby exerting an anti-inflammatory effect. It was recently discovered that T-cell immunoglobulin mucin domain 1 (Tim-1) is essential for maintaining Bregs function related to immune tolerance. However, the detailed understanding of Tim-1+ Bregs and IL-10+ Bregs in T1D patients is lacking. This study aimed to characterize the profile of B cell subsets in T1D patients compared with that in controls and determine whether Tim-1+ Bregs and IL-10+ Bregs play roles in T1D.
A total of 47 patients with T1D, 30 patients with type 2 diabetes (T2D) and 24 healthy controls were recruited in this study. Flow cytometry was used to measure the levels of different B cell subsets (including B cells, plasmablasts, and Bregs) in the peripheral blood. Radiobinding assays were performed to detect the antibody titres of T1D patients. In addition, the correlations between different B cell subsets and patient parameters were investigated.
Compared with healthy controls, differences in frequency of Tim-1+ Bregs were significantly decreased in patients with T1D (36.53 ± 6.51 vs. 42.25 ± 6.83, P=0.02*), and frequency of IL-10+ Bregs were lower than healthy controls (17.64 ± 7.21vs. 24.52 ± 11.69, P=0.009**), the frequency of total Bregs in PBMC was also decreased in patients with T1D (1.42 ± 0.53vs. 1.99 ± 0.93, P=0.002.**). We analyzed whether these alterations in B cells subsets were associated with clinical features. The frequencies of Tim-1+ Bregs and IL-10+ Bregs were negatively related to fasting blood glucose (FBG) (r=-0.25 and -0.22; P=0.01* and 0.03*, respectively). The frequencies of Tim-1+ Bregs and IL-10+ Bregs are positively correlated with fast C-peptide (FCP) (r=0.23 and 0.37; P=0.02* and 0.0001***, respectively). In addition, the frequency of IL-10+ Breg was also negatively related to glycosylated haemoglobin (HbA1c) (r=-0.20, P=0.04*). The frequencies of Tim-1+ Bregs, IL-10+ Bregs and Bregs in T2D patients were reduced, but no statistically significant difference was found between other groups. Interestingly, there was positive correlation between the frequencies of Tim-1+ Bregs and IL-10+ Bregs in T1D (r=0.37, P=0.01*). Of note, it is worth noting that our study did not observe any correlations between B cell subsets and autoantibody titres.
Our study showed altered Tim-1 and IL-10 expression in regulatory B cell in T1D patients. Tim-1, as suggested by the present study, is associated with islet function and blood glucose levels. These findings indicate that Tim-1+ Bregs and IL-10+ Bregs were involved in the pathogenesis of T1D.
A total of 47 patients with T1D, 30 patients with type 2 diabetes (T2D) and 24 healthy controls were recruited in this study. Flow cytometry was used to measure the levels of different B cell subsets (including B cells, plasmablasts, and Bregs) in the peripheral blood. Radiobinding assays were performed to detect the antibody titres of T1D patients. In addition, the correlations between different B cell subsets and patient parameters were investigated.
Compared with healthy controls, differences in frequency of Tim-1+ Bregs were significantly decreased in patients with T1D (36.53 ± 6.51 vs. 42.25 ± 6.83, P=0.02*), and frequency of IL-10+ Bregs were lower than healthy controls (17.64 ± 7.21vs. 24.52 ± 11.69, P=0.009**), the frequency of total Bregs in PBMC was also decreased in patients with T1D (1.42 ± 0.53vs. 1.99 ± 0.93, P=0.002.**). We analyzed whether these alterations in B cells subsets were associated with clinical features. The frequencies of Tim-1+ Bregs and IL-10+ Bregs were negatively related to fasting blood glucose (FBG) (r=-0.25 and -0.22; P=0.01* and 0.03*, respectively). The frequencies of Tim-1+ Bregs and IL-10+ Bregs are positively correlated with fast C-peptide (FCP) (r=0.23 and 0.37; P=0.02* and 0.0001***, respectively). In addition, the frequency of IL-10+ Breg was also negatively related to glycosylated haemoglobin (HbA1c) (r=-0.20, P=0.04*). The frequencies of Tim-1+ Bregs, IL-10+ Bregs and Bregs in T2D patients were reduced, but no statistically significant difference was found between other groups. Interestingly, there was positive correlation between the frequencies of Tim-1+ Bregs and IL-10+ Bregs in T1D (r=0.37, P=0.01*). Of note, it is worth noting that our study did not observe any correlations between B cell subsets and autoantibody titres.
Our study showed altered Tim-1 and IL-10 expression in regulatory B cell in T1D patients. Tim-1, as suggested by the present study, is associated with islet function and blood glucose levels. These findings indicate that Tim-1+ Bregs and IL-10+ Bregs were involved in the pathogenesis of T1D.
摘要：
1型糖尿病（T1D）是一种病因复杂的自身免疫性疾病。B细胞在T1D的发病机制中起重要作用。调节性B细胞（Bregs）是产生和分泌抑制因子白细胞介素-10（IL-10）的B细胞的一个子集，从而发挥抗炎作用。最近发现T细胞免疫球蛋白粘蛋白结构域1（Tim-1）对于维持与免疫耐受相关的Bregs功能至关重要。然而,缺乏对T1D患者Tim-1+Bregs和IL-10+Bregs的详细了解。这项研究旨在表征T1D患者与对照组相比的B细胞亚群分布，并确定Tim-1Bregs和IL-10Bregs是否在T1D中起作用。
共有47例T1D患者，本研究招募了30名2型糖尿病（T2D）患者和24名健康对照。流式细胞术用于测量不同B细胞亚群（包括B细胞，成浆细胞,和Bregs）在外周血中。进行放射结合测定以检测T1D患者的抗体滴度。此外,研究了不同B细胞亚群与患者参数之间的相关性.
与健康对照相比，T1D患者的Tim-1+Bregs频率差异显着降低（36.53±6.51vs.42.25±6.83,P=0.02*),IL-10+Bregs的频率低于健康对照组（17.64±7.21vs.24.52±11.69,P=0.009**),T1D患者PBMC中总Bregs的频率也降低(1.42±0.53vs.1.99±0.93,P=0.002。**).我们分析了B细胞亚群的这些改变是否与临床特征相关。Tim-1+Bregs和IL-10+Bregs的频率与空腹血糖（FBG）呈负相关（r=-0.25和-0.22；P=0.01*和0.03*，分别)。Tim-1+Bregs和IL-10+Bregs的频率与快速C肽（FCP）呈正相关（r=0.23和0.37；P=0.02*和0.0001***，分别)。此外,IL-10+Breg的频率也与糖化血红蛋白（HbA1c）呈负相关（r=-0.20，P=0.04*）。Tim-1+Bregs的频率,IL-10+Bregs和Bregs在T2D患者中降低，但其他组间差异无统计学意义。有趣的是,T1D中Tim-1+Bregs和IL-10+Bregs的频率呈正相关（r=0.37，P=0.01*）。值得注意的是，值得注意的是,我们的研究未观察到B细胞亚群与自身抗体滴度之间存在任何相关性.
我们的研究显示T1D患者调节性B细胞中Tim-1和IL-10表达的改变。根据本研究的建议，Tim-1，与胰岛功能和血糖水平有关。这些发现表明Tim-1+Bregs和IL-10+Bregs参与了T1D的发病机制。
共有47例T1D患者，本研究招募了30名2型糖尿病（T2D）患者和24名健康对照。流式细胞术用于测量不同B细胞亚群（包括B细胞，成浆细胞,和Bregs）在外周血中。进行放射结合测定以检测T1D患者的抗体滴度。此外,研究了不同B细胞亚群与患者参数之间的相关性.
与健康对照相比，T1D患者的Tim-1+Bregs频率差异显着降低（36.53±6.51vs.42.25±6.83,P=0.02*),IL-10+Bregs的频率低于健康对照组（17.64±7.21vs.24.52±11.69,P=0.009**),T1D患者PBMC中总Bregs的频率也降低(1.42±0.53vs.1.99±0.93,P=0.002。**).我们分析了B细胞亚群的这些改变是否与临床特征相关。Tim-1+Bregs和IL-10+Bregs的频率与空腹血糖（FBG）呈负相关（r=-0.25和-0.22；P=0.01*和0.03*，分别)。Tim-1+Bregs和IL-10+Bregs的频率与快速C肽（FCP）呈正相关（r=0.23和0.37；P=0.02*和0.0001***，分别)。此外,IL-10+Breg的频率也与糖化血红蛋白（HbA1c）呈负相关（r=-0.20，P=0.04*）。Tim-1+Bregs的频率,IL-10+Bregs和Bregs在T2D患者中降低，但其他组间差异无统计学意义。有趣的是,T1D中Tim-1+Bregs和IL-10+Bregs的频率呈正相关（r=0.37，P=0.01*）。值得注意的是，值得注意的是,我们的研究未观察到B细胞亚群与自身抗体滴度之间存在任何相关性.
我们的研究显示T1D患者调节性B细胞中Tim-1和IL-10表达的改变。根据本研究的建议，Tim-1，与胰岛功能和血糖水平有关。这些发现表明Tim-1+Bregs和IL-10+Bregs参与了T1D的发病机制。
