Publication: Papel de la fosfatasa de regeneración hepática 1 (PRL-1) durante el ensamblaje de la sinapsis inmunológica y la activación de los linfocitos T
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2018-11-21
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Universidad Complutense de Madrid
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Abstract
Los linfocitos CD4 naíf se diferencian a distintos subtipos de células efectoras Th (Th1, Th2, Th17 y Treg) tras ser estimulados por células presentadoras de antígeno (APCs) en el ganglio linfático. Las células Th generadas migran a la periferia, donde un segundo encuentro con el mismo antígeno presentado por APCs conducirá a su activación y función efectora. Tanto la activación inicial de la célula naíf en el ganglio como la reactivación de la célula efectora en la periferia tienen lugar en el contexto de la sinapsis inmunológica (IS), un contacto dinámico y especializado entre una APC y un linfocito. El contacto inicial entre el linfocito T y la APC ocurre en el lamelipodio, donde la estimulación del receptor de la célula T (TCR) y la señalización a través de moléculas de adhesión y de coestimulación induce reordenamientos en el citoesqueleto que estabilizan el contacto, conduciendo a la formación de una IS madura. La estimulación por TCR y moléculas coestimuladoras desencadena redes de señalización que conducen a la activación del linfocito T y su función efectora. La dinámica de actina juega un papel fundamental tanto en el establecimiento de la IS como en la progresión de la señalización necesaria para alcanzar la completa activación del linfocito T.
Stimulation of naïve CD4 T cells in the lymph node by antigen presenting cells (APCs) induces their differentiation into effector T helper (Th) cells. Effector Th cells then migrate to peripheral sites, where a secondary encounter with the same antigen presented by APCs will lead to their activation and effector function, including secretion of appropriate cytokines. Both the initial activation of naïve cells in the lymph node and the reactivation of effector cells in the periphery take place in the context of the immunological synapse (IS). The IS is a specialized dynamic contact between an APC and a lymphocyte. Initial contact between a migrating T cell and an APC takes place at the leading lamellipodium, where T cell receptor (TCR) engagement and signaling through adhesion and costimulatory molecules induces cytoskeletal rearrangements that stabilize the contact, leading to the formation of a mature IS. Recognition of the antigen by the TCR, together with costimulation, triggers the activation of signaling networks that lead to full T cell activation and effector function. Actin dynamics play a central role in both the establishment of the IS and the progression of sustained signaling required for full T cell activation...
Stimulation of naïve CD4 T cells in the lymph node by antigen presenting cells (APCs) induces their differentiation into effector T helper (Th) cells. Effector Th cells then migrate to peripheral sites, where a secondary encounter with the same antigen presented by APCs will lead to their activation and effector function, including secretion of appropriate cytokines. Both the initial activation of naïve cells in the lymph node and the reactivation of effector cells in the periphery take place in the context of the immunological synapse (IS). The IS is a specialized dynamic contact between an APC and a lymphocyte. Initial contact between a migrating T cell and an APC takes place at the leading lamellipodium, where T cell receptor (TCR) engagement and signaling through adhesion and costimulatory molecules induces cytoskeletal rearrangements that stabilize the contact, leading to the formation of a mature IS. Recognition of the antigen by the TCR, together with costimulation, triggers the activation of signaling networks that lead to full T cell activation and effector function. Actin dynamics play a central role in both the establishment of the IS and the progression of sustained signaling required for full T cell activation...
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Tesis de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 20-12-2017