Lymph node homeostasis and adaptation to immune challenge resolved by fibroblast network mechanics.

Autor: Horsnell HL; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, London, UK., Tetley RJ; Tissue Mechanics Group, MRC Laboratory for Molecular Cell Biology, University College London, London, UK., De Belly H; Physiological Laboratory, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK., Makris S; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, London, UK., Millward LJ; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, London, UK., Benjamin AC; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, London, UK., Heeringa LA; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, London, UK., de Winde CM; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, London, UK., Paluch EK; Physiological Laboratory, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK., Mao Y; Tissue Mechanics Group, MRC Laboratory for Molecular Cell Biology, University College London, London, UK.; Institute for the Physics of Living Systems, University College London, London, UK., Acton SE; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, London, UK. s.acton@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2022 Aug; Vol. 23 (8), pp. 1169-1182. Date of Electronic Publication: 2022 Jul 26.
DOI: 10.1038/s41590-022-01272-5
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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