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La Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC) es la mayor institución pública dedicada a la investigación en España y la tercera de Europa. Adscrita al Ministerio de Economía y Competitividad, a través de la Secretaría de Estado de Investigación, Desarrollo e Innovación, su objetivo fundamental es desarrollar y promover investigaciones en beneficio del progreso científico y tecnológico, para lo cual está abierta a la colaboración con entidades españolas y extranjeras. El CSIC desempeña un papel central en la política científica y tecnológica, ya que abarca desde la investigación básica a la transferencia del conocimiento al sector productivo. El motor de la investigación lo forman sus centros e institutos, distribuidos por todas las comunidades autónomas, y sus más de 15.000 trabajadores, de los cuales más de 3.000 son investigadores en plantilla y otros tantos doctores y científicos en formación. El CSIC cuenta con el 6 por ciento del personal dedicado a la Investigación y el Desarrollo en España, que genera aproximadamente el 20 por ciento de la producción científica nacional. Además, gestiona un conjunto de importantes infraestructuras, la red más completa y extensa de bibliotecas especializadas y cuenta con unidades mixtas de investigación. http://www.csic.es/

Descifran cómo se producen las células dendríticas en el timo humano

Fuente: CSIC | Publicado: 31-10-2017
Investigadores del Centro de Biología Molecular Severo Ochoa, centro mixto de la Universidad Autónoma de Madrid (UAM) y el Consejo Superior de Investigaciones Científicas (CSIC), han aportado una nueva visión de la función del timo como órgano hematopoyético productor, no sólo de los linfocitos T como se sabía, sino de células dendríticas. En el timo, estas células inducen la tolerancia inmunológica y evitan la autoinmunidad.
Derechos: Expresión de Notch Jagged1 en la región medular del timo humano. Izda.: Distribución de Notch Jagged1 (rojo) y de células epiteliales tímicas (verde) en región medular (M) y cortical (C). Dcha.: Localización anatómica de células dendríticas (rojo). /UAM
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Las células dendríticas son células del sistema inmunitario, que se originan en la médula ósea y que migran a los órganos periféricos para ejercer su función durante las respuestas inmunitarias. Este tipo de células han sido identificadas en el timo, un órgano hematopoyético distinto de la médula ósea cuya función principal es la producción de los linfocitos T, las células del sistema inmunitario esenciales para la defensa frente a microorganismos.



En el timo, las células dendríticas realizan una función crucial en el proceso de aprendizaje de los linfocitos T: permiten establecer la tolerancia central frente a los antígenos propios y evitan el desarrollo de enfermedades autoinmunes. A pesar de esta relevante función, el origen de las células dendríticas intratímicas ha sido hasta ahora desconocido, lo que ha generado un intenso debate sobre su posible generación en el timo.


Un estudio reciente, llevado a cabo por investigadores del Centro de Biología Molecular Severo Ochoa, centro mixto de la Universidad Autónoma de Madrid (UAM) y el Consejo Superior de Investigaciones Científicas (CSIC), ha demostrado que, efectivamente, las células dendríticas pueden generarse en el timo humano a partir de las mismas células que se encargan de la producción de los linfocitos T.


El estudio, publicado en el Journal of Experimental Medicine, describe además el mecanismo molecular responsable de la generación diferencial de células dendríticas o linfocitos T en el timo humano, a partir de una célula progenitora común.


Un progenitor común para linfocitos T y células dendríticas


Los científicos, dirigidos por María Luisa Toribio del CSIC, emplearon cultivos primarios de una única célula, ensayos in vivo con ratones inmunodeficientes y técnicas de citometría de flujo y de microscopía confocal de rastreo de alta cobertura. De este modo, lograron establecer que las células más inmaduras del timo humano generan linfocitos T o células dendríticas, dependiendo de las señales que reciben en el nicho intratímico en el que se localizan.



“Hemos demostrado que la expresión diferencial en la médula tímica de Jagged1, un ligando de la familia de receptores Notch, proporciona el nicho selectivo que induce la generación de células dendríticas a partir de un progenitor común, estando implicado en el proceso el factor de transcripción GATA2”, describe Toribio.


“Por el contrario –detalla la investigadora– los ligandos Delta-like distribuidos a través de la corteza del timo, evitan la generación de células dendríticas e inducen la generación de linfocitos T a expensas de las mismas. La identificación en el timo de precursores de células dendríticas en distintas etapas de su proceso madurativo proporciona evidencia directa de la función del timo como un órgano hematopoyético para este tipo de células, adicional a la médula ósea”.


El trabajo contó con la colaboración de investigadores del Centro Nacional de Microbiología del Instituto de Salud Carlos III, así como de profesionales del Centro Nacional de Investigaciones Cardiovasculares, el Hospital Universitario La Paz y el Hospital Universitario 12 de Octubre de Madrid, y ha sido financiado por el Plan Nacional del Ministerio de Economía y Competitividad y el 7º Programa Marco de la Unión Europea.


Referencia bibliográfica: Enrique Martín-Gayo, Sara González-García, María J. García-León, Alba Murcia- Ceballos, Juan Alcain, Marina García-Peydró, Luis Allende, Belén de Andrés, María L. Gaspar and María L. Toribio. “Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches”. Journal of Experimental Medicine. DOI: 10.1084/jem.20161564
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