Lores Pablo, Costa Monique, Saravia Anderson, Landeira Mercedes, da Costa Valeria, Rodríguez-Zraquia Santiago A, Cedrés M Eugenia, Oliva Juan, Rado Guillermina, García Ignacio, Festari M Florencia, Consani Sandra, Díaz Carolina, Freire Teresa
Laboratorio de Inmunomodulación y Vacunas, Unidad Académica de Inmunobiología, Facultad de Medicina, Universidad de la República, Uruguay; Unidad de Enfermedades Autoinmunes Sistémicas del Hospital Maciel, Unidades Académicas Médicas 1 y 3, ASSE, Facultad de Medicina, Universidad de la República, Uruguay.
Laboratorio de Inmunomodulación y Vacunas, Unidad Académica de Inmunobiología, Facultad de Medicina, Universidad de la República, Uruguay.
Immunol Lett. 2025 Dec;276:107052. doi: 10.1016/j.imlet.2025.107052. Epub 2025 Jun 8.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by severe joint inflammation, synovial hyperplasia and degradation of the cartilage and bone in the joint. Patients with RA have an amplified T helper (Th) 1 and Th17 immune response and production of autoantibodies by autoreactive B cells. In the joint, macrophages mediate bone destruction and maintain the inflammatory process in RA. There is an increasing body of evidence indicating that NADPH oxidase (NOX2)-derived reactive oxygen species (ROS), mainly produced by macrophages and neutrophils, may have effector functions in RA. In this work we characterized ROS production in both monocytes and macrophages in RA. Our results indicate that NOX2-dependent production of ROS attenuates inflammation and clinical signs by decreasing innate and adaptive immune responses in collagen-induced arthritis in mice. We also report that ROS production by circulating classical and non-classical monocytes from patients with RA negatively correlate with disease symptoms. Therefore, ROS produced by different monocyte subsets in peripheral blood might be considered as useful biomarkers or predictors of the immune response associated with RA disease activity.
类风湿性关节炎(RA)是一种慢性自身免疫性疾病,其特征为严重的关节炎症、滑膜增生以及关节软骨和骨骼的退化。RA患者具有增强的辅助性T(Th)1和Th17免疫反应,以及自身反应性B细胞产生自身抗体。在关节中,巨噬细胞介导骨破坏并维持RA中的炎症过程。越来越多的证据表明,主要由巨噬细胞和中性粒细胞产生的烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶(NOX2)衍生的活性氧(ROS)可能在RA中发挥效应功能。在这项研究中,我们对RA患者单核细胞和巨噬细胞中的ROS产生进行了表征。我们的结果表明,在小鼠胶原诱导的关节炎中,NOX2依赖性ROS产生通过降低先天性和适应性免疫反应来减轻炎症和临床症状。我们还报告称,RA患者循环中的经典和非经典单核细胞产生的ROS与疾病症状呈负相关。因此,外周血中不同单核细胞亚群产生的ROS可能被视为与RA疾病活动相关的免疫反应的有用生物标志物或预测指标。