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Dendritic cells control fibroblastic reticular network tension and lymph node expansion.
Acton, Sophie E; Farrugia, Aaron J; Astarita, Jillian L; Mourão-Sá, Diego; Jenkins, Robert P; Nye, Emma; Hooper, Steven; van Blijswijk, Janneke; Rogers, Neil C; Snelgrove, Kathryn J; Rosewell, Ian; Moita, Luis F; Stamp, Gordon; Turley, Shannon J; Sahai, Erik; Reis e Sousa, Caetano.
Afiliación
  • Acton SE; 1] 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.
  • Farrugia AJ; 1] Immunobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK [2] Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • Astarita JL; Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
  • Mourão-Sá D; Immunobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • Jenkins RP; Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • Nye E; Experimental Histopathology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • Hooper S; Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • van Blijswijk J; Immunobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • Rogers NC; Immunobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • Snelgrove KJ; Immunobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • Rosewell I; Transgenics Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Potters Bar, Hertfordshire EN6 3LD, UK.
  • Moita LF; 1] Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal [2] Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
  • Stamp G; Experimental Histopathology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • Turley SJ; Department of Cancer Immunology, Genentech, One DNA Way, South San Francisco, California 94080, USA.
  • Sahai E; Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • Reis e Sousa C; Immunobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Nature ; 514(7523): 498-502, 2014 Oct 23.
Article en En | MEDLINE | ID: mdl-25341788
After immunogenic challenge, infiltrating and dividing lymphocytes markedly increase lymph node cellularity, leading to organ expansion. Here we report that the physical elasticity of lymph nodes is maintained in part by podoplanin (PDPN) signalling in stromal fibroblastic reticular cells (FRCs) and its modulation by CLEC-2 expressed on dendritic cells. We show in mouse cells that PDPN induces actomyosin contractility in FRCs via activation of RhoA/C and downstream Rho-associated protein kinase (ROCK). Engagement by CLEC-2 causes PDPN clustering and rapidly uncouples PDPN from RhoA/C activation, relaxing the actomyosin cytoskeleton and permitting FRC stretching. Notably, administration of CLEC-2 protein to immunized mice augments lymph node expansion. In contrast, lymph node expansion is significantly constrained in mice selectively lacking CLEC-2 expression in dendritic cells. Thus, the same dendritic cells that initiate immunity by presenting antigens to T lymphocytes also initiate remodelling of lymph nodes by delivering CLEC-2 to FRCs. CLEC-2 modulation of PDPN signalling permits FRC network stretching and allows for the rapid lymph node expansion--driven by lymphocyte influx and proliferation--that is the critical hallmark of adaptive immunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Células del Estroma / Fibroblastos / Ganglios Linfáticos Límite: Animals Idioma: En Revista: Nature Año: 2014 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Células del Estroma / Fibroblastos / Ganglios Linfáticos Límite: Animals Idioma: En Revista: Nature Año: 2014 Tipo del documento: Article Pais de publicación: Reino Unido