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Conduit Integrity is Compromised During Acute Lymph Node Expansion

48 Pages Posted: 20 Feb 2019 Publication Status: Review Complete

See all articles by Victor G. Martinez

Victor G. Martinez

University College London - Stromal Immunology Group

Valeriya Pankova

University College London - Stromal Immunology Group

Lukas Krasny

Institute of Cancer Research (ICR) - Division of Molecular Pathology

Tanya Singh

University College London - Bioinformatics Image Core

Ian J. White

University College London - Electron Microscopy Facility

Agnesska C. Benjamin

University College London - Stromal Immunology Group

Simone Dertschnig

University College London - UCL Institute of Immunity and Transplantation

Harry L. Horsnell

University College London - Stromal Immunology Group

Janos Kriston-Vizi

University College London - Bioinformatics Image Core

Jemima J. Burden

University College London - Electron Microscopy Facility

Paul H. Huang

Institute of Cancer Research (ICR) - Division of Molecular Pathology

Christopher J. Tape

University College London - Cell Communication Lab

Sophie Acton

University College London - Stromal Immunology Group

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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 3-5-fold expansion during each adaptive immune response but these ECM-rich structures are not permanently damaged. Whether conduit integrity and filtering function is affected during LN expansion is unknown. Here we show that conduits are disrupted during acute LN expansion but FRC-FRC contacts remain connected. We reveal that polarised FRCs deposit ECM basolaterally utilising 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, but flow becomes leaky, allowing soluble molecules increased access to antigen-presenting cells. We show how dynamic communication between peripheral tissues and LNs changes during immune responses, and describe a mechanism enabling LNs to prevent inflammation-induced fibrosis.

Keywords: Fibroblastic reticular network, Conduit, Extracellular matrix, Lymph node, Pleckstrin Homology Like Domain Family B Member 2 (LL5-b)

Suggested Citation

Martinez, Victor G. and Pankova, Valeriya and Krasny, Lukas and Singh, Tanya and White, Ian J. and Benjamin, Agnesska C. and Dertschnig, Simone and Horsnell, Harry L. and Kriston-Vizi, Janos and Burden, Jemima J. and Huang, Paul H. and Tape, Christopher J. and Acton, Sophie, Conduit Integrity is Compromised During Acute Lymph Node Expansion (February 15, 2019). Available at SSRN: https://ssrn.com/abstract=3334979 or http://dx.doi.org/10.2139/ssrn.3334979
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Victor G. Martinez

University College London - Stromal Immunology Group

Gower Street
London, WC1E 6BT
United Kingdom

Valeriya Pankova

University College London - Stromal Immunology Group

Gower Street
London, WC1E 6BT
United Kingdom

Lukas Krasny

Institute of Cancer Research (ICR) - Division of Molecular Pathology

123 Old Brompton Road
London, England SW7 3RP
United Kingdom

Tanya Singh

University College London - Bioinformatics Image Core

Gower Street
London, WC1E 6BT
United Kingdom

Ian J. White

University College London - Electron Microscopy Facility

Gower Street
London, WC1E 6BT
United Kingdom

Agnesska C. Benjamin

University College London - Stromal Immunology Group

Gower Street
London, WC1E 6BT
United Kingdom

Simone Dertschnig

University College London - UCL Institute of Immunity and Transplantation

Gower Street
London, WC1E 6BT
United Kingdom

Harry L. Horsnell

University College London - Stromal Immunology Group

Gower Street
London, WC1E 6BT
United Kingdom

Janos Kriston-Vizi

University College London - Bioinformatics Image Core

Gower Street
London, WC1E 6BT
United Kingdom

Jemima J. Burden

University College London - Electron Microscopy Facility

Gower Street
London, WC1E 6BT
United Kingdom

Paul H. Huang

Institute of Cancer Research (ICR) - Division of Molecular Pathology

123 Old Brompton Road
London, England SW7 3RP
United Kingdom

Christopher J. Tape

University College London - Cell Communication Lab

Gower Street
London, WC1E 6BT
United Kingdom

Sophie Acton (Contact Author)

University College London - Stromal Immunology Group ( email )

Gower Street
London, WC1E 6BT
United Kingdom

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