研究动态
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CD19+ CD5+ CD1d+ Bregs在SLE合并动脉粥样硬化小鼠中维持Th17/Treg平衡的作用。

Role of CD19+ CD5+ CD1d+ Bregs in maintaining the Th17/Treg balance in mice with systemic lupus erythematosus complicated with atherosclerosis.

发表日期:2023 Apr 03
作者: Zhen-Zhen Zhu, Xiao-Huan Chen, Si-Ru Wei, Jia Xu, Ya-Hui Wang, Wen-Jue Wu, Hong Liu, Han-You Mo
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

在这项研究中,我们旨在调查Breg对Th17/Treg细胞平衡的调节作用以及在低密度脂蛋白受体(LDLr)-/-  + Pristane小鼠模型中下游炎症因子的释放情况。在建立SLE合并动脉粥样硬化(AS)的小鼠模型后,将8周龄的LDLr-/-  + Pristane小鼠(n = 10)纳入SLE + AS组。此外,以8周龄的MRL/lpr小鼠和C57小鼠分别作为SLE和正常对照组(每组n = 10)。饲喂高脂饮食14周后,收集小鼠的外周血和脾脏,通过流式细胞术、酶联免疫吸附法和逆转录聚合酶链反应检测Breg、Th17和Treg细胞以及相关的炎性因子。SLE + AS小鼠脾淋巴细胞中Breg和Treg的数量显著下降,而Th17细胞的数量显著增加,与C57组相比(p <.05)。此外,Breg的比例与Th17/Treg比值呈负相关(p =.03)。SLE + AS组的小鼠血清中IL-10、IL-17和肿瘤坏死因子-α的水平较SLE和C57组显著升高(p <.05)。此外,SLE + AS组中IL-35和转化生长因子(TGF)-β的表达相对于C57组减少(p <.05)。Breg减少的比例与Th17/Treg增加呈负相关,这在SLE + AS小鼠中增加了,表明Breg可能通过产生IL-35和TGF-β来调节Th17/Treg细胞的平衡和细胞因子的释放。©2023亚太风湿病协会联合会和Wiley&Sons Australia,有限公司。
In this study, we aimed to investigate Bregs, their regulatory effects on Th17/Treg cell balance, and the release of downstream inflammatory factors in a mouse model of low-density lipoprotein receptor (LDLr)-/-  + Pristane.After the establishment of the mouse model of systemic lupus erythematosus (SLE) complicated with atherosclerosis (AS), 8-week-old LDLr-/-  + Pristane mice (n = 10) were included in the SLE + AS group. Furthermore, 8-week-old MRL/lpr and C57 mice were used as the SLE and normal control groups, respectively (n = 10 per group). After feeding the mice a high-fat diet for 14 weeks, peripheral blood and spleen of mice were collected, and Bregs, Th17, and Treg cells and related inflammatory factors were detected by flow cytometry, enzyme-linked immunosorbent assay, and reverse-transcription polymerase chain reaction.The number of Bregs and Tregs in spleen lymphocytes of SLE + AS mice significantly decreased compared with the C57 group (p < .05), whereas the number of Th17 cells significantly increased (p = .000). Furthermore, the proportion of Bregs showed a negative correlation with the Th17/Treg ratio (p = .03). Mice in the SLE + AS group showed higher serum interleukin (IL)-10, IL-17, and tumor necrosis factor-α levels than those in the SLE and C57 groups (p < .05). Furthermore, IL-35 and transforming growth factor (TGF)-β expression was reduced in the SLE + AS group compared with the C57 group (p < .05).The proportion of Breg decreases was negatively associated with increased Th17/Treg which was increased in SLE + AS mice, indicating that Bregs may regulate Th17/Treg cell homeostasis and cytokine release via IL-35 and TGF-β production.© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.