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Topological Small-World Organization of the Fibroblastic Reticular Cell Network Determines Lymph Node Functionality.
Novkovic, Mario; Onder, Lucas; Cupovic, Jovana; Abe, Jun; Bomze, David; Cremasco, Viviana; Scandella, Elke; Stein, Jens V; Bocharov, Gennady; Turley, Shannon J; Ludewig, Burkhard.
Afiliación
  • Novkovic M; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Onder L; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Cupovic J; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Abe J; Theodor Kocher Institute, University of Bern, Bern, Switzerland.
  • Bomze D; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Cremasco V; Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States of America.
  • Scandella E; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Stein JV; Theodor Kocher Institute, University of Bern, Bern, Switzerland.
  • Bocharov G; Institute of Numerical Mathematics, Russian Academy of Sciences, Moscow, Russia.
  • Turley SJ; Department of Cancer Immunology, Genentech, South San Francisco, California, United States of America.
  • Ludewig B; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
PLoS Biol ; 14(7): e1002515, 2016 07.
Article en En | MEDLINE | ID: mdl-27415420
ABSTRACT
Fibroblastic reticular cells (FRCs) form the cellular scaffold of lymph nodes (LNs) and establish distinct microenvironmental niches to provide key molecules that drive innate and adaptive immune responses and control immune regulatory processes. Here, we have used a graph theory-based systems biology approach to determine topological properties and robustness of the LN FRC network in mice. We found that the FRC network exhibits an imprinted small-world topology that is fully regenerated within 4 wk after complete FRC ablation. Moreover, in silico perturbation analysis and in vivo validation revealed that LNs can tolerate a loss of approximately 50% of their FRCs without substantial impairment of immune cell recruitment, intranodal T cell migration, and dendritic cell-mediated activation of antiviral CD8+ T cells. Overall, our study reveals the high topological robustness of the FRC network and the critical role of the network integrity for the activation of adaptive immune responses.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfocitos T / Comunicación Celular / Movimiento Celular / Fibroblastos / Ganglios Linfáticos Límite: Animals Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Suiza

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfocitos T / Comunicación Celular / Movimiento Celular / Fibroblastos / Ganglios Linfáticos Límite: Animals Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Suiza