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

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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:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Abe, Jun and Stein, Jens Volker

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1544-9173

Publisher:

Public Library of Science

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

22 May 2017 13:52

Last Modified:

28 May 2017 02:16

Publisher DOI:

10.1371/journal.pbio.1002515

PubMed ID:

27415420

BORIS DOI:

10.7892/boris.95385

URI:

https://boris.unibe.ch/id/eprint/95385

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