Department of Rheumatology, Guilin Medical University, Guilin, Guangxi, China.
Department of Endocrinology and Rheumatology, The First People's Hospital of Linping District, Hangzhou, China.
Int J Rheum Dis. 2023 Jun;26(6):1048-1057. doi: 10.1111/1756-185X.14691. Epub 2023 Apr 3.
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.
本研究旨在探讨 B regs 在低密度脂蛋白受体（LDLr）+Pristane 小鼠模型中对 Th17/Treg 细胞平衡的调节作用及其下游炎症因子的释放。
建立系统性红斑狼疮（SLE）合并动脉粥样硬化（AS）小鼠模型后，将 8 周龄 LDLr+Pristane 小鼠（n=10）纳入 SLE+AS 组。此外，将 8 周龄 MRL/lpr 和 C57 小鼠分别作为 SLE 和正常对照组（每组 n=10）。高脂饮食喂养 14 周后，收集小鼠外周血和脾脏，采用流式细胞术、酶联免疫吸附试验和逆转录聚合酶链反应检测 Bregs、Th17 和 Treg 细胞及相关炎症因子。
与 C57 组相比，SLE+AS 组小鼠脾脏淋巴细胞中 Bregs 和 Treg 细胞数量明显减少（p<0.05），而 Th17 细胞数量明显增加（p=0.000）。此外，Bregs 比例与 Th17/Treg 比值呈负相关（p=0.03）。SLE+AS 组小鼠血清白细胞介素（IL）-10、IL-17 和肿瘤坏死因子-α水平明显高于 SLE 组和 C57 组（p<0.05）。此外，与 C57 组相比，SLE+AS 组小鼠血清 IL-35 和转化生长因子（TGF）-β表达降低（p<0.05）。
SLE+AS 小鼠中 Breg 比例的降低与 Th17/Treg 比值的增加呈负相关，表明 Breg 可能通过产生 IL-35 和 TGF-β 来调节 Th17/Treg 细胞的稳态和细胞因子的释放。
