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Multi-tier mechanics control stromal adaptations in swelling lymph nodes

View ORCID ProfileFrank P. Assen, Miroslav Hons, View ORCID ProfileRobert Hauschild, Shayan Shamipour, View ORCID ProfileJun Abe, Walter A. Kaufmann, Tommaso Costanzo, View ORCID ProfileGabriel Krens, Markus Brown, View ORCID ProfileBurkhard Ludewig, View ORCID ProfileSimon Hippenmeyer, View ORCID ProfileJens V. Stein, View ORCID ProfileCarl-Philipp Heisenberg, View ORCID ProfileEdouard Hannezo, View ORCID ProfileSanjiv A. Luther, View ORCID ProfileMichael Sixt
doi: https://doi.org/10.1101/2021.07.28.454217
Frank P. Assen
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
2Department of Dermatology, Medical University Vienna, Vienna, Austria
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  • For correspondence: Sixt@ist.ac.at frank.assen@meduniwien.ac.at
Miroslav Hons
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
3BIOCEV, First Faculty of Medicine, Charles University, Vestec, Czech Republic
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Robert Hauschild
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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Shayan Shamipour
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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Jun Abe
4Department of Oncology, Microbiology and Immunology, University of Fribourg, Fribourg, Switzerland
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Walter A. Kaufmann
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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Tommaso Costanzo
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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Gabriel Krens
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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Markus Brown
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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Burkhard Ludewig
5Institute of Immunobiology, Kantonsspital St Gallen, St Gallen, Switzerland
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  • ORCID record for Burkhard Ludewig
Simon Hippenmeyer
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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Jens V. Stein
4Department of Oncology, Microbiology and Immunology, University of Fribourg, Fribourg, Switzerland
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Carl-Philipp Heisenberg
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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  • ORCID record for Carl-Philipp Heisenberg
Edouard Hannezo
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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Sanjiv A. Luther
6Department of Biochemistry, University of Lausanne, Epalinges, Switzerland
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Michael Sixt
1Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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  • For correspondence: Sixt@ist.ac.at frank.assen@meduniwien.ac.at
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Abstract

Lymph nodes (LNs) comprise two main structural elements: Fibroblastic reticular cells (FRCs) that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. While LNs are fairly stable in size during homeostatic conditions, immunological challenge causes more than 10-fold increase in size within only a few days. How a solid organ can accommodate such extreme volumetric changes is poorly understood. Here, we characterize the biomechanics of LN swelling on the cellular and organ scale. We identify lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing FRCs and their associated conduits to stretch. After an initial phase of relaxation, FRCs sense the resulting strain via cell matrix adhesions, which coordinates local growth and remodeling of the stromal network. While the expanded FRC network adopts its typical configuration, a massive fibrotic reaction of the organ capsule sets in and counters further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multi-tier fashion.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted July 29, 2021.
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Multi-tier mechanics control stromal adaptations in swelling lymph nodes
Frank P. Assen, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Jun Abe, Walter A. Kaufmann, Tommaso Costanzo, Gabriel Krens, Markus Brown, Burkhard Ludewig, Simon Hippenmeyer, Jens V. Stein, Carl-Philipp Heisenberg, Edouard Hannezo, Sanjiv A. Luther, Michael Sixt
bioRxiv 2021.07.28.454217; doi: https://doi.org/10.1101/2021.07.28.454217
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Multi-tier mechanics control stromal adaptations in swelling lymph nodes
Frank P. Assen, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Jun Abe, Walter A. Kaufmann, Tommaso Costanzo, Gabriel Krens, Markus Brown, Burkhard Ludewig, Simon Hippenmeyer, Jens V. Stein, Carl-Philipp Heisenberg, Edouard Hannezo, Sanjiv A. Luther, Michael Sixt
bioRxiv 2021.07.28.454217; doi: https://doi.org/10.1101/2021.07.28.454217

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