Fibroblastic Reticular Cells Control Conduit Matrix Deposition during Lymph Node Expansion.
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Date
2019-11-26Author
Martinez, VG
Pankova, V
Krasny, L
Singh, T
Makris, S
White, IJ
Benjamin, AC
Dertschnig, S
Horsnell, HL
Kriston-Vizi, J
Burden, JJ
Huang, PH
Tape, CJ
Acton, SE
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Lymph Nodes
Extracellular Matrix
Fibroblasts
Research team
Oncogene
Molecular and Systems Oncology
Language
eng
Date accepted
2019-10-25
License start date
2019-11
Citation
Cell reports, 2019, 29 (9), pp. 2810 - 2822.e5
Publisher
CELL PRESS