*Department of Pathology and Immunology, Medical Faculty and University of Geneva, 1211 Geneva 4, Switzerland.
†Geneva University Hospital, 1211 Geneva 4, Switzerland.
Clin Sci (Lond). 2015 May 1;128(10):635-48. doi: 10.1042/CS20140635.
The phagocyte NADPH oxidase NOX2 produces reactive oxygen species (ROS) and is a well-known player in host defence. However, there is also increasing evidence for a regulatory role of NOX2 in adaptive immunity. Deficiency in phagocyte NADPH oxidase causes chronic granulomatous disease (CGD) in humans, a condition that can also be studied in CGD mice. Clinical observations in CGD patients suggest a higher susceptibility to autoimmune diseases, in particular lupus, idiopathic thrombocytopenic purpura and rheumatoid arthritis. In mice, a strong correlation exists between a polymorphism in a NOX2 subunit and the development of autoimmune arthritis. NOX2 deficiency in mice also favours lupus development. Both CGD patients and CGD mice exhibit increased levels of immunoglobulins, including autoantibodies. Despite these phenotypes suggesting a role for NOX2 in specific immunity, mechanistic explanations for the typical increase of CGD in autoimmune disease and antibody levels are still preliminary. NOX2-dependent ROS generation is well documented for dendritic cells and B-lymphocytes. It is unclear whether T-lymphocytes produce ROS themselves or whether they are exposed to ROS derived from dendritic cells during the process of antigen presentation. ROS are signalling molecules in virtually any cell type, including T- and B-lymphocytes. However, knowledge about the impact of ROS-dependent signalling on T- and B-lymphocyte phenotype and response is still limited. ROS might contribute to Th1/Th2/Th17 cell fate decisions during T-lymphocyte activation and might enhance immunoglobulin production by B-lymphocytes. In dendritic cells, NOX2-derived ROS might be important for antigen processing and cell activation.
吞噬细胞 NADPH 氧化酶 NOX2 产生活性氧 (ROS)，是宿主防御的重要参与者。然而，NOX2 在适应性免疫中的调节作用也有越来越多的证据。吞噬细胞 NADPH 氧化酶缺乏会导致人类慢性肉芽肿病 (CGD)，CGD 小鼠也可用于研究该疾病。CGD 患者的临床观察表明，他们更容易患自身免疫性疾病，特别是狼疮、特发性血小板减少性紫癜和类风湿性关节炎。在小鼠中，NOX2 亚基的一种多态性与自身免疫性关节炎的发展之间存在很强的相关性。NOX2 缺乏也有利于狼疮的发展。CGD 患者和 CGD 小鼠都表现出免疫球蛋白水平升高，包括自身抗体。尽管这些表型表明 NOX2 在特异性免疫中起作用，但 CGD 自身免疫病和抗体水平升高的机制解释仍处于初步阶段。NOX2 依赖性 ROS 的产生在树突状细胞和 B 淋巴细胞中已有很好的记载。目前还不清楚 T 淋巴细胞本身是否产生 ROS，或者它们在抗原呈递过程中是否暴露于来自树突状细胞的 ROS。ROS 是几乎任何细胞类型（包括 T 和 B 淋巴细胞）中的信号分子。然而，关于 ROS 依赖性信号对 T 和 B 淋巴细胞表型和反应的影响的知识仍然有限。ROS 可能在 T 淋巴细胞激活过程中对 Th1/Th2/Th17 细胞命运决定起作用，并可能增强 B 淋巴细胞的免疫球蛋白产生。在树突状细胞中，NOX2 衍生的 ROS 可能对抗原处理和细胞激活很重要。
