Publication: Papel de los receptores EphB2 y EphB3 en el desarrollo tímico temprano
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2017-06-22
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Universidad Complutense de Madrid
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Abstract
El timo es un órgano linfoide primario responsable del desarrollo funcional de las células T inmunocompetentes. Está compuesto, principalmente, por dos elementos: el epitelio tímico (TEC) y las células linfoides cuyos progenitores colonizan el primordio del órgano alrededor del día 11.5F (Gordon y cols., 2004). Ambos componentes organizan en el timo adulto dos áreas histológica y funcionalmente diferenciadas, corteza y médula, donde acontece la selección positiva y negativa, respectivamente, de los receptores antigénicos de los timocitos en desarrollo, claves para la funcionalidad inmune (Blackburn y Manley, 2004). La maduración del epitelio y los timocitos conlleva interacciones célula a célula en la que estudios anteriores de nuestro grupo habían implicado a los receptores tirosina quinasa Eph y sus ligandos, las ephrinas, y más concretamente, a las EphB2 y EphB3. Nuestros estudios recientemente resumidos (Garcia‐Ceca y cols., 2015) relacionan estas moléculas con muchos de los procesos que suceden en el timo, pero no clarifica su origen durante la ontogenia del órgano ni los componentes celulares y moleculares específicamente implicados. Curiosamente, en ausencia de EphB2 o EphB3 los timos son hipoplásicos (Alfaro y cols., 2008) y muestran profundas alteraciones en la red epitelial que empiezan pronto en el desarrollo (Garcia‐Ceca y cols., 2009a), pero muchos menos defectos en el componente linfoide (Alfaro y cols., 2008)...
The thymus is a primary lymphoid organ concerned with the functional development of immunocompetent T cells. It consists, principally, of two cellular components: the thymic epithelium (TEC) and the lymphoid cells, whose progenitor cells colonize the thymic primordium around E11.5 (Gordon et al., 2004). Both components organize in the thymus two histological and functionally different areas, named cortex and medulla, in which positive and negative selection respectively, of the antigen receptors of developing thymocytes occurs. Both processes are key for reaching the immune functionality (Blackburn y Manley, 2004). The maturation of the two thymic components, epithelium and thymocytes, implies cell‐to‐cell interactions. Our own previous studies had demonstrated the relevance of tyrosine kinase receptors Eph and their ligands, the ephrins; concretely, of EphB2 and EphB3 in that process. Our studies associate these molecules with many of the functional events occurring in the thymus (Garcia‐Ceca et al., 2015), but they do not determine when this involvement appears during ontogeny neither the concrete cell types and molecules involved. Remarkably, the lack of EphB2 or EphB3 results in hypoplastic thymuses (Alfaro et al., 2008) exhibiting important alterations of the epithelial cell network that appear early in ontogeny (Garcia‐Ceca et al., 2009a) and a less severe lymphoid phenotype (Alfaro et al., 2008)...
The thymus is a primary lymphoid organ concerned with the functional development of immunocompetent T cells. It consists, principally, of two cellular components: the thymic epithelium (TEC) and the lymphoid cells, whose progenitor cells colonize the thymic primordium around E11.5 (Gordon et al., 2004). Both components organize in the thymus two histological and functionally different areas, named cortex and medulla, in which positive and negative selection respectively, of the antigen receptors of developing thymocytes occurs. Both processes are key for reaching the immune functionality (Blackburn y Manley, 2004). The maturation of the two thymic components, epithelium and thymocytes, implies cell‐to‐cell interactions. Our own previous studies had demonstrated the relevance of tyrosine kinase receptors Eph and their ligands, the ephrins; concretely, of EphB2 and EphB3 in that process. Our studies associate these molecules with many of the functional events occurring in the thymus (Garcia‐Ceca et al., 2015), but they do not determine when this involvement appears during ontogeny neither the concrete cell types and molecules involved. Remarkably, the lack of EphB2 or EphB3 results in hypoplastic thymuses (Alfaro et al., 2008) exhibiting important alterations of the epithelial cell network that appear early in ontogeny (Garcia‐Ceca et al., 2009a) and a less severe lymphoid phenotype (Alfaro et al., 2008)...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Biología Celular, leída el 19-12-2016