Fibroblastic Reticular Cells Control Conduit Matrix Deposition during Lymph Node Expansion
Victor G. Martinez,
Valeriya Pankova,
Lukas Krasny,
Tanya Singh,
Spyridon Makris,
Ian J. White,
Agnesska C. Benjamin,
Simone Dertschnig,
Harry L. Horsnell,
Janos Kriston-Vizi,
Jemima J. Burden,
Paul H. Huang,
Christopher J. Tape,
Sophie E. Acton
Affiliations
Victor G. Martinez
Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK
Valeriya Pankova
Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK
Lukas Krasny
Division of Molecular Pathology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
Tanya Singh
Bioinformatics Image Core, MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK
Spyridon Makris
Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK
Ian J. White
Electron Microscopy Facility, MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK
Agnesska C. Benjamin
Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK
Simone Dertschnig
UCL Institute of Immunity and Transplantation, University College London, London NW3 2PF, UK
Harry L. Horsnell
Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK
Janos Kriston-Vizi
Bioinformatics Image Core, MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK
Jemima J. Burden
Electron Microscopy Facility, MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK
Paul H. Huang
Division of Molecular Pathology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
Christopher J. Tape
Cell Communication Lab, Department of Oncology, University College London Cancer Institute, 72 Huntley Street, London WC1E 6DD, UK
Sophie E. Acton
Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK; Corresponding author
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. : Fibroblastic reticular cells control matrix production for lymph node conduit function. Martinez et al. show that matrix production is reduced and conduit flow is altered during lymph node expansion. Matrix deposition by fibroblastic reticular cells is controlled by CLEC-2/podoplanin signaling and directed unilaterally into conduit structures by LL5-β-tethered microtubules. Keywords: lymph node, conduit, extracellular matrix, fibroblastic reticular cells, microtubules, pleckstrin homology-like domain family B member 2, podoplanin, CLEC-2, polarity
