Diverse cellular and organismal functions of the lysosomal thiol reductase GILT.
Diverse cellular and organismal functions of the lysosomal thiol reductase GILT.
复制标题
DOI：
10.1016/j.molimm.2015.06.008
复制
发表时间：
2015-12
影响因子：
3.6
通讯作者：
Hastings KT
中科院分区：
文献类型：
--
作者：
Rausch MP;Hastings KT
γ-干扰素诱导型溶酶体巯基还原酶（GILT）是已知的唯一催化内吞途径中二硫键还原的酶。GILT促进来自含二硫键抗原的表位子集的呈递。MHC II类限制性表位的增强呈递改变了中枢耐受性并调节了CD 4 + T细胞介导的自身免疫病毒表位的改进的交叉呈递导致病毒特异性CD 8 + T细胞的改进的交叉引发。GILT调节细胞的氧化还原状态。在GILT−/−细胞中，谷胱甘肽从还原型转变为氧化型，导致线粒体自噬，超氧化物歧化酶2减少，超氧化物水平升高。GILT表达减少细胞活化，包括磷酸化ERK 1/2减少，并降低细胞增殖。GILT增强细菌溶血素（如溶血素O）的活性，并增加细菌复制和感染。GILT在癌细胞中的表达与改善的患者存活率相关。GILT的这些不同的角色进行了讨论。
Gamma-interferon-inducible lysosomal thiol reductase (GILT) is the only enzyme known to catalyze disulfide bond reduction in the endocytic pathway. GILT facilitates the presentation of a subset of epitopes from disulfide bond-containing antigens. Enhanced presentation of MHC class II-restricted epitopes alters central tolerance and modulates CD4+ T cell-mediated autoimmunity. Improved cross-presentation of viral epitopes results in improved cross-priming of viral-specific CD8+ T cells. GILT regulates the cellular redox state. In GILT−/− cells, there is a shift from the reduced to the oxidized form of glutathione, resulting in mitochondrial autophagy, decreased superoxide dismutase 2, and elevated superoxide levels. GILT expression diminishes cellular activation, including decreased phosphorylated ERK1/2, and decreases cellular proliferation. GILT enhances the activity of bacterial hemolysins, such as listeriolysin O, and increases bacterial replication and infection. GILT expression in cancer cells is associated with improved patient survival. These diverse roles of GILT are discussed.