Redox remodeling as an immunoregulatory strategy.
Redox remodeling as an immunoregulatory strategy.
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DOI：
10.1021/bi902022n
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发表时间：
2010-02-16
期刊：
影响因子：
2.9
通讯作者：
Banerjee, Ruma
中科院分区：
文献类型：
--
作者：
Yan, Zhonghua;Banerjee, Ruma
T细胞的活化和增殖需要免疫突触中由抗原呈递细胞特别是树突状细胞提供的还原性细胞外微环境。T细胞对树突状细胞的刺激激活树突状细胞中的NF-κB通路并诱导抗氧化反应。它还增强系统xc依赖的胱氨酸摄取，导致谷胱甘肽合成增加，输出，最后，降解为细胞外的半胱氨酸。细胞外半胱氨酸的积累支持T细胞中的谷胱甘肽合成，同时还导致T细胞增殖所需的更还原的氧化还原电位。天然存在的调节性T细胞是T细胞的抑制亚群，通过抑制自身反应性效应T细胞来预防自身免疫性疾病并维持外周耐受。它们还抑制对寄生虫，病毒和肿瘤的有益免疫反应。然而，它们的抑制机制仍不完全清楚。最近，我们发现，抑制调节性T细胞的树突状细胞诱导的细胞外氧化还原重塑是调节性T细胞抑制机制的一个组成部分。在这篇综述中，我们描述了最近的进展，我们的理解氧化还原调节和信号转导的适应性免疫系统的重点是T细胞激活树突状细胞。调节性T细胞在扰乱树突状细胞的氧化还原重塑的作用及其作为一般的调节性T细胞抑制机制的影响进行了讨论。
Activation and proliferation of T cells require a reducing extracellular microenvironment in the immune synapse that is provided by antigen presenting cells especially dendritic cells. Stimulation of dendritic cells by T cells activates the NF-κB pathway in dendritic cells and induces an antioxidant response. It also enhances system xc--dependent cystine uptake, leading to increased glutathione synthesis, export and finally, degradation to cysteine outside the cell. Accumulation of extracellular cysteine supports glutathione synthesis in T cells while also leading to a more reducing redox potential that is needed for T cell proliferation. Naturally occurring regulatory T cells, a suppressor sub-population of T cells, prevent autoimmune diseases and maintain peripheral tolerance by suppressing self-reactive effector T cells. They also suppress beneficial immune responses to parasites, viruses and tumors. However, their mechanism of suppression is still not fully understood. Recently, we have found that inhibition by regulatory T cells of dendritic cell-induced extracellular redox remodeling is a component of the regulatory T cell suppression mechanism. In this review, we describe recent advances in our understanding of redox regulation and signaling in the adaptive immune system with a focus on T cell activation by dendritic cells. The role of regulatory T cells in perturbing redox remodeling by dendritic cells and its implications as a general regulatory T cell suppression mechanism are discussed.
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影响因子：
2.3
作者：
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作者：
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发表时间：
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影响因子：
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作者：
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