Division of Medical Biochemistry, Biocenter, Medical University, Innsbruck, Austria.
Redox Rep. 2013;18(3):88-94. doi: 10.1179/1351000213Y.0000000044. Epub 2013 Apr 19.
Reactive oxygen and nitrogen species (ROS-RNS) and other redox active molecules fulfill key functions in immunity. Beside the initiation of cytocidal reactions within the pathogen defense strategy, redox reactions trigger and shape the immune response and are further involved in termination and initialization of cellular restorative processes. Regulatory mechanisms provided by redox-activated signaling events guarantee the correct spatial and temporal proceeding of immunological processes, and continued imbalances in redox homeostasis lead to crucial failures of control mechanisms, thus promoting the development of pathological conditions. Interferon-gamma is the most potent inducer of ROS-RNS formation in target cells like macrophages. Immune-regulatory pathways such as tryptophan breakdown via indoleamine 2,3-dioxygenase and neopterin production by GTP-cyclohydrolase-I are initiated during T helper cell type 1 (Th1-type) immune response concomitant to the production of ROS-RNS by immunocompetent cells. Therefore, increased neopterin production and tryptophan breakdown is representative of an activated cellular immune system and can be used for the in vivo and in vitro monitoring of oxidative stress. In parallel, the activation of the redox-sensitive transcription factor nuclear factor-kappa B is a central element in immunity leading to cell type and stimulus-specific expression of responsive genes. Furthermore, T cell activation and proliferation are strongly dependent on the redox potential of the extracellular microenvironment. T cell commitment to Th1, Th2, regulatory T cell, and other phenotypes appears to crucially depend on the activation of redox-sensitive signaling cascades, where oxidative conditions support Th1 development while 'antioxidative' stress leads to a shift to allergic Th2-type immune responses.
活性氧和氮物种 (ROS-RNS) 以及其他氧化还原活性分子在免疫中发挥关键作用。除了在病原体防御策略中启动细胞毒性反应外，氧化还原反应还触发和塑造免疫反应，并进一步参与细胞修复过程的终止和初始化。由氧化还原激活的信号事件提供的调节机制保证了免疫过程的正确时空进行，而氧化还原稳态的持续失衡导致关键的控制机制失效，从而促进病理状况的发展。干扰素-γ是巨噬细胞等靶细胞中 ROS-RNS 形成的最有效诱导剂。免疫调节途径，如色氨酸通过吲哚胺 2,3-双加氧酶分解和 GTP-环化水解酶-I 产生新喋呤，在 T 辅助细胞 1（Th1 型）免疫反应期间与免疫细胞产生 ROS-RNS 同时启动。因此，增加的新喋呤产生和色氨酸分解是激活细胞免疫系统的代表，可以用于体内和体外氧化应激的监测。平行地，氧化还原敏感转录因子核因子-κB 的激活是免疫的一个中心要素，导致响应基因的细胞类型和刺激特异性表达。此外，T 细胞的激活和增殖强烈依赖于细胞外微环境的氧化还原电位。T 细胞向 Th1、Th2、调节性 T 细胞和其他表型的承诺似乎严重依赖于氧化还原敏感信号级联的激活，其中氧化条件支持 Th1 发育，而“抗氧化”应激导致向过敏 Th2 型免疫反应的转变。
