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PLoS One ; 8(2): e52368, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23468835

RESUMEN

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 ß1 integrin ligand fibronectin, and to polarize appropriately in response to fibronectin and VCAM-1 binding. This defect was specific for ß1 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 ß1 integrin function and homing to lymphoid organs.


Asunto(s)
Proteínas del Citoesqueleto/genética , Tejido Linfoide/metabolismo , Proteínas de Microfilamentos/genética , Linfocitos T/metabolismo , Animales , Adhesión Celular/genética , Quimiotaxis/genética , Quimiotaxis/inmunología , Proteínas del Citoesqueleto/metabolismo , Integrina beta1/metabolismo , Ligandos , Tejido Linfoide/inmunología , Ratones , Ratones Transgénicos , Proteínas de Microfilamentos/deficiencia , Proteínas de Microfilamentos/metabolismo , Receptores CCR7/metabolismo , Linfocitos T/inmunología , Migración Transendotelial y Transepitelial/ética , Migración Transendotelial y Transepitelial/genética
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