Cell Reports
Volume 29, Issue 9, 26 November 2019, Pages 2810-2822.e5
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Article
Fibroblastic Reticular Cells Control Conduit Matrix Deposition during Lymph Node Expansion

https://doi.org/10.1016/j.celrep.2019.10.103Get rights and content
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Highlights

  • Conduit flow becomes locally intermittent during lymph node expansion

  • Fibroblastic reticular cells use polarized microtubules to guide matrix deposition

  • The CLEC-2/PDPN signaling axis controls conduit matrix composition

  • Fibroblastic reticular cells reduce matrix production during lymph node expansion

Summary

Lymph nodes (LNs) act as filters, constantly sampling peripheral cues. This is facilitated by the conduit network, a tubular structure of aligned extracellular matrix (ECM) fibrils ensheathed by fibroblastic reticular cells (FRCs). LNs undergo rapid 3- to 5-fold expansion during adaptive immune responses, but these ECM-rich structures are not permanently damaged. Whether conduit flow or filtering function is affected during LN expansion is unknown. Here, we show that conduits are partially disrupted during acute LN expansion, but FRC-FRC contacts remain connected. We reveal that polarized FRCs deposit ECM basolaterally using LL5-β and that ECM production is regulated at transcriptional and secretory levels by the C-type lectin CLEC-2, expressed by dendritic cells. Inflamed LNs maintain conduit size exclusion, and flow is disrupted but persists, indicating the robustness of this structure despite rapid tissue expansion. We show how dynamic communication between peripheral tissues and LNs provides a mechanism to prevent inflammation-induced fibrosis in lymphoid tissue.

Keywords

lymph node
conduit
extracellular matrix
fibroblastic reticular cells
microtubules
pleckstrin homology-like domain family B member 2
podoplanin
CLEC-2
polarity

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