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 Volker; Bocharov, Gennady; Turley, Shannon J; Ludewig, Burkhard (2016). Topological Small-World Organization of the Fibroblastic Reticular Cell Network Determines Lymph Node Functionality. PLoS biology, 14(7), e1002515. Public Library of Science 10.1371/journal.pbio.1002515

Preview

Text journal.pbio.1002515.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (5MB) | Preview

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.

Interest & Impact

Downloads

149 since deposited on 22 May 2017
21 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item