Lymph node homeostasis and adaptation to immune challenge resolved by fibroblast network mechanics View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-07-26

AUTHORS

Harry L. Horsnell, Robert J. Tetley, Henry De Belly, Spyridon Makris, Lindsey J. Millward, Agnesska C. Benjamin, Lucas A. Heeringa, Charlotte M. de Winde, Ewa K. Paluch, Yanlan Mao, Sophie E. Acton

ABSTRACT

Emergent physical properties of tissues are not readily understood by reductionist studies of their constituent cells. Here, we show molecular signals controlling cellular, physical, and structural properties and collectively determine tissue mechanics of lymph nodes, an immunologically relevant adult tissue. Lymph nodes paradoxically maintain robust tissue architecture in homeostasis yet are continually poised for extensive expansion upon immune challenge. We find that in murine models of immune challenge, cytoskeletal mechanics of a cellular meshwork of fibroblasts determine tissue tension independently of extracellular matrix scaffolds. We determine that C-type lectin-like receptor 2 (CLEC-2)–podoplanin signaling regulates the cell surface mechanics of fibroblasts, providing a mechanically sensitive pathway to regulate lymph node remodeling. Perturbation of fibroblast mechanics through genetic deletion of podoplanin attenuates T cell activation. We find that increased tissue tension through the fibroblastic stromal meshwork is required to trigger the initiation of fibroblast proliferation and restore homeostatic cellular ratios and tissue structure through lymph node expansion. More... »

PAGES

1169-1182

References to SciGraph publications

  • 2014-08-24. B cell homeostasis and follicle confines are governed by fibroblastic reticular cells in NATURE IMMUNOLOGY
  • 2020-01-24. A framework for advancing our understanding of cancer-associated fibroblasts in NATURE REVIEWS CANCER
  • 2017-05-19. Systematic comparison of 2A peptides for cloning multi-genes in a polycistronic vector in SCIENTIFIC REPORTS
  • 2018-02-24. Intravital Imaging of Dynamic Bone and Immune Systems, Methods and Protocols in NONE
  • 2022-04-01. Interplay between mechanics and signalling in regulating cell fate in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2014-10-27. The CLEC-2–podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture in NATURE IMMUNOLOGY
  • 2020-03-23. Lymph node stromal cells: cartographers of the immune system in NATURE IMMUNOLOGY
  • 2021-05-10. A biomechanical switch regulates the transition towards homeostasis in oesophageal epithelium in NATURE CELL BIOLOGY
  • 2007-09-23. Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells in NATURE IMMUNOLOGY
  • 2018-10. CRISPR/Cas9-mediated knockout of Rag-2 causes systemic lymphopenia with hypoplastic lymphoid organs in FVB mice in LABORATORY ANIMAL RESEARCH
  • 2012-04-01. Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks in NATURE IMMUNOLOGY
  • 2013-09-01. Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2 in NATURE
  • 2008-05-23. The actin cytoskeleton in cancer cell motility in CLINICAL & EXPERIMENTAL METASTASIS
  • 2019-08-19. The physics of cell-size regulation across timescales in NATURE PHYSICS
  • 2017-05-31. Multiscale force sensing in development in NATURE CELL BIOLOGY
  • 2014-10-22. Dendritic cells control fibroblastic reticular network tension and lymph node expansion in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41590-022-01272-5

    DOI

    http://dx.doi.org/10.1038/s41590-022-01272-5

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35882934


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    29 schema:description Emergent physical properties of tissues are not readily understood by reductionist studies of their constituent cells. Here, we show molecular signals controlling cellular, physical, and structural properties and collectively determine tissue mechanics of lymph nodes, an immunologically relevant adult tissue. Lymph nodes paradoxically maintain robust tissue architecture in homeostasis yet are continually poised for extensive expansion upon immune challenge. We find that in murine models of immune challenge, cytoskeletal mechanics of a cellular meshwork of fibroblasts determine tissue tension independently of extracellular matrix scaffolds. We determine that C-type lectin-like receptor 2 (CLEC-2)–podoplanin signaling regulates the cell surface mechanics of fibroblasts, providing a mechanically sensitive pathway to regulate lymph node remodeling. Perturbation of fibroblast mechanics through genetic deletion of podoplanin attenuates T cell activation. We find that increased tissue tension through the fibroblastic stromal meshwork is required to trigger the initiation of fibroblast proliferation and restore homeostatic cellular ratios and tissue structure through lymph node expansion.
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