Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.
Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.
复制标题
酪氨酸磷酸酶调节 TCR 信号转导：从自身免疫到免疫治疗。
DOI：
10.3389/fcell.2020.608747
复制
发表时间：
2020
影响因子：
5.5
通讯作者：
Zamoyska R
中科院分区：
文献类型：
--
作者：
Castro-Sanchez P;Teagle AR;Prade S;Zamoyska R
早期的TCR信号依赖于多种信号和接头蛋白的快速磷酸化和去磷酸化，导致T细胞的激活。这一过程受到蛋白激酶和磷酸酶之间错综复杂的相互作用网络的严格调控。许多酪氨酸磷酸酶已被证明通过负调控早期TCR信号来调节T细胞的反应，从而改变T细胞的命运。其中一些酶的突变与人类自身免疫易感性的增强有关，而缺乏同源基因的小鼠模型经常显示T细胞过度激活。因此，在需要增强T细胞反应的情况下，磷酸酶正在成为潜在的靶点，例如对肿瘤的免疫反应。在这篇综述中，我们总结了调控早期TCR信号的酪氨酸磷酸酶的现有知识，并讨论了它们在自身免疫中的作用以及它们作为肿瘤免疫治疗靶点的可能性。
Early TCR signaling is dependent on rapid phosphorylation and dephosphorylation of multiple signaling and adaptor proteins, leading to T cell activation. This process is tightly regulated by an intricate web of interactions between kinases and phosphatases. A number of tyrosine phosphatases have been shown to modulate T cell responses and thus alter T cell fate by negatively regulating early TCR signaling. Mutations in some of these enzymes are associated with enhanced predisposition to autoimmunity in humans, and mouse models deficient in orthologous genes often show T cell hyper-activation. Therefore, phosphatases are emerging as potential targets in situations where it is desirable to enhance T cell responses, such as immune responses to tumors. In this review, we summarize the current knowledge about tyrosine phosphatases that regulate early TCR signaling and discuss their involvement in autoimmunity and their potential as targets for tumor immunotherapy.