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Las células dendríticas controlan la tensión de la red reticular fibroblástica y la expansión de los ganglios

Sophie E Acton¹, Aaron J Farrugia², Jillian L Astarita³

¹1] Immunobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK [2] Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.

|October 25, 2014

Resumen

La expansión de los ganglios linfáticos durante la inmunidad depende de la podoplanina (PDPN) y la señalización CLEC-2. Las células dendríticas usan CLEC-2 para relajar PDPN en las células reticulares fibroblásticas (FRC), permitiendo que los ganglios linfáticos crezcan.

Área de la Ciencia:

Inmunología Inmunología.
Biología celular Biología celular.
La biofísica es la biofísica.

Sus antecedentes:

La expansión de los ganglios linfáticos es un sello distintivo de la inmunidad adaptativa, impulsada por la proliferación y la afluencia de linfocitos.
Las propiedades físicas y la elasticidad de los ganglios linfáticos son cruciales para acomodar esta expansión.
Las células reticulares fibroblásticas stromales (FRC) forman la red de ganglios linfáticos, influyendo en sus propiedades mecánicas.

Objetivo del estudio:

Investigar el papel de la podoplanina (PDPN) y la señalización CLEC-2 en la regulación de la elasticidad y la expansión de los ganglios linfáticos.
Para dilucidar los mecanismos moleculares por los cuales las células dendríticas modulan el comportamiento FRC durante las respuestas inmunes.

Principales métodos:

Estudios in vitro utilizando células de ratón para analizar las vías de señalización mediadas por PDPN.
Experimentos in vivo con ratones genéticamente modificados que carecen de CLEC-2 en las células dendríticas.
Administración de la proteína CLEC-2 a ratones inmunizados de tipo salvaje.

Principales resultados:

La señalización de la podoplanina (PDPN) en los FRC induce la contractilidad de la actomiosina a través de RhoA/C y ROCK.
CLEC-2 expresado por células dendríticas se une a PDPN, causando agrupación y desacoplamiento de RhoA / C, lo que lleva a la relajación de FRC.
La administración de CLEC-2 mejoró la expansión de los ganglios linfáticos en ratones inmunizados.
La pérdida de CLEC-2 en las células dendríticas limitó significativamente la expansión de los ganglios linfáticos.

Conclusiones:

Las células dendríticas remodelan activamente los ganglios linfáticos mediante la modulación de la señalización PDPN en los FRC a través de CLEC-2.
Esta interacción CLEC-2/PDPN permite el estiramiento de la red FRC, facilitando la rápida expansión de los ganglios linfáticos esencial para la inmunidad adaptativa.

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