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Isolation of Murine Lymph Node Stromal Cells
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Multitier mechanics control stromal adaptations in the swelling lymph node.

Frank P Assen1,2, Jun Abe3, Miroslav Hons4,5

  • 1Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria. frank.assen@meduniwien.ac.at.

Nature Immunology
|July 11, 2022
PubMed
Summary

Lymph nodes (LNs) swell rapidly during immune responses due to lymphocyte accumulation. Fibroblastic reticular cells (TRCs) and capsular fibroblasts coordinate this mechanical process through strain sensing and fibrotic reactions.

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Area of Science:

  • Immunology
  • Cell Biology
  • Biophysics

Background:

  • Lymph nodes (LNs) are crucial for immune responses, exhibiting significant size increases upon immunological challenge.
  • LNs consist of fibroblastic reticular cells (TRCs) forming immune cell niches and capsular fibroblasts forming the organ's outer shell.

Purpose of the Study:

  • To investigate the biomechanics of lymph node swelling at both cellular and organ levels.
  • To understand the roles of different fibroblast populations in regulating LN size changes during immune responses.

Main Methods:

  • Characterization of cellular and organ-scale biomechanics during LN swelling.
  • Analysis of lymphocyte trapping, proliferation, and resulting pressure forces.
  • Investigation of TRC strain sensing, cell-matrix adhesions, and stromal network remodeling.
  • Assessment of the fibrotic reaction in the organ capsule.

Main Results:

  • Lymphocyte influx and proliferation generate outward pressure, stretching TRCs and their associated conduits.
  • TRCs sense mechanical strain, initiating coordinated growth and remodeling of the stromal network.
  • Following an initial relaxation phase, the TRC network readopts its configuration.
  • A significant fibrotic reaction in the organ capsule limits further LN expansion.

Conclusions:

  • Lymph node swelling is a multi-tiered mechanical process controlled by distinct fibroblast populations.
  • TRCs and capsular fibroblasts play coordinated but distinct roles in managing LN size changes.
  • Understanding these biomechanical processes offers insights into immune regulation and tissue remodeling.