Fibroblastic Reticular Cells Control Conduit Matrix Deposition during Lymph Node Expansion.
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Embargo End Date
ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2019-11-26
Date Accepted
2019-10-25
Abstract
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.
Citation
Cell reports, 2019, 29 (9), pp. 2810 - 2822.e5
Source Title
Publisher
CELL PRESS
ISSN
2211-1247
eISSN
2211-1247
Collections
Research Team
Oncogene
Molecular and Systems Oncology
Molecular and Systems Oncology