Ezrin and moesin are required for efficient T cell adhesion and homing to lymphoid organs.
Ezrin and moesin are required for efficient T cell adhesion and homing to lymphoid organs.
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DOI：
10.1371/journal.pone.0052368
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Burkhardt JK
中科院分区：
文献类型：
--
作者：
Chen EJ;Shaffer MH;Williamson EK;Huang Y;Burkhardt JK
T细胞在血液和淋巴器官之间的运输是一个复杂的多步骤过程，需要细胞结构中的几个高度动态和协调的变化。肌动蛋白结合蛋白的ezrin，radixin和moesin（ERM）家族的成员已被牵连在这个过程的几个方面，但研究产生了相互矛盾的结果。使用在CD 4+细胞和膜突蛋白特异性siRNA中有条件缺失ezrin的小鼠，我们产生了缺乏ERM蛋白的T细胞，并研究了对T细胞运输所需的特定事件的影响。ERM缺陷型T细胞在多个体外和体内试验中迁移正常，并能在体外进行有效的渗出。然而，这些细胞粘附于β1整联蛋白配体纤连蛋白的能力受损，并且响应于纤连蛋白和VCAM-1结合而适当粘附的能力受损。这种缺陷对β1整合素是特异性的，因为对ICAM-1的粘附和极化反应是正常的。在体内，ERM缺陷型T细胞在归巢淋巴器官方面表现出缺陷。综上所述，这些结果表明，ERM蛋白在很大程度上与T细胞趋化性无关，但对β1整联蛋白功能和归巢淋巴器官很重要。
T cell trafficking between the blood and lymphoid organs is a complex, multistep process that requires several highly dynamic and coordinated changes in cyto-architecture. Members of the ezrin, radixin and moesin (ERM) family of actin-binding proteins have been implicated in several aspects of this process, but studies have yielded conflicting results. Using mice with a conditional deletion of ezrin in CD4+ cells and moesin-specific siRNA, we generated T cells lacking ERM proteins, and investigated the effect on specific events required for T cell trafficking. ERM-deficient T cells migrated normally in multiple in vitro and in vivo assays, and could undergo efficient diapedesis in vitro. However, these cells were impaired in their ability to adhere to the β1 integrin ligand fibronectin, and to polarize appropriately in response to fibronectin and VCAM-1 binding. This defect was specific for β1 integrins, as adhesion and polarization in response to ICAM-1 were normal. In vivo, ERM-deficient T cells showed defects in homing to lymphoid organs. Taken together, these results show that ERM proteins are largely dispensable for T cell chemotaxis, but are important for β1 integrin function and homing to lymphoid organs.
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影响因子：
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