Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwaro, Daejeon 35015, Korea.
Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 266 Munhwaro, Daejeon 35015, Korea.
Int J Mol Sci. 2021 Nov 17;22(22):12411. doi: 10.3390/ijms222212411.
The production and oxidation mechanism of reactive oxygen species (ROS) are out of balance in rheumatoid arthritis (RA). However, the correlation between ROS and T cell subsets in RA remains unclear. Peripheral blood mononuclear cells (PBMCs) from patients with RA (n = 40) and healthy controls (n = 10) were isolated from whole blood samples. Synovial tissues (n = 3) and synovial fluid (n = 10) were obtained from patients with RA. The repartition of T cell subsets and expression of ROS and cytokines were examined according to RA severity. Fibroblast-like synoviocytes (FLSs) from patients with RA were stimulated with PBMCs and the expression of inflammation-related molecules were measured by RT-PCR and cytokine array. Regulatory T cells from patients with moderate (5.1 > DAS28 ≥ 3.2) RA showed the highest expression of mitochondrial ROS among the groups based on disease severity. Although ROS levels steadily increased with RA severity, there was a slight decline in severe RA (DAS28 ≥ 5.1) compared with moderate RA. The expression of inflammatory cytokines in RA FLSs were significantly inhibited when FLSs were co-cultured with PBMCs treated with ROS inhibitor. These findings provide a novel approach to suppress inflammatory response of FLSs through ROS regulation in PBMCs.
类风湿关节炎 (RA) 中活性氧 (ROS) 的产生和氧化机制失去平衡。然而，ROS 与 RA 中 T 细胞亚群之间的相关性尚不清楚。从 RA 患者 (n = 40) 和健康对照者 (n = 10) 的全血样本中分离外周血单核细胞 (PBMC)。从 RA 患者中获得滑膜组织 (n = 3) 和滑液 (n = 10)。根据 RA 严重程度检查 T 细胞亚群的分布以及 ROS 和细胞因子的表达。用 PBMC 刺激 RA 患者的成纤维样滑膜细胞 (FLS)，并通过 RT-PCR 和细胞因子阵列测量炎症相关分子的表达。根据疾病严重程度，中度 (5.1>DAS28≥3.2) RA 患者的调节性 T 细胞的线粒体 ROS 表达最高。尽管 ROS 水平随着 RA 严重程度的增加而稳定增加，但与中度 RA 相比，重度 RA (DAS28≥5.1) 略有下降。当用 ROS 抑制剂处理的 PBMC 与 FLS 共培养时，RA FLS 中的炎症细胞因子的表达显著受到抑制。这些发现为通过 PBMC 中 ROS 调节抑制 FLS 的炎症反应提供了一种新方法。
