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Topological Small-World Organization of the Fibroblastic Reticular Cell Network Determines Lymph Node Functionality

Novkovic, Mario and Onder, Lucas and Cupovic, Jovana and Abe, Jun and Bomze, David and Cremasco, Viviana and Scandella, Elke and Stein, Jens and Bocharov, Jennadi and Turley, Shannon and Ludewig, Burkhard (2016) Topological Small-World Organization of the Fibroblastic Reticular Cell Network Determines Lymph Node Functionality. PLoS Biology, 14 (7). ISSN 1545-7885

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.

Item Type: Article
Date Deposited: 29 Nov 2017 00:45
Last Modified: 25 Jan 2019 00:45
URI: https://oak.novartis.com/id/eprint/28385

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