AI Article Synopsis

  • Lymph nodes have a complex structure that affects how lymphocytes (a type of immune cell) move, but the mechanisms behind their movement are still not well understood.
  • Lymphatic fibroblastic reticular cells (FRCs) produce lysophosphatidic acid (LPA), which interacts with T-cells through the LPA2 receptor to enhance their motility within the lymph node.
  • Research shows that disrupting LPA production or the LPA2 receptor in T-cells significantly reduces their ability to move inside lymph nodes, indicating that LPA is crucial for T-cell movement through tight spaces in the lymphatic environment.

Article Abstract

Lymph nodes (LNs) are highly confined environments with a cell-dense three-dimensional meshwork, in which lymphocyte migration is regulated by intracellular contractile proteins. However, the molecular cues directing intranodal cell migration remain poorly characterized. Here we demonstrate that lysophosphatidic acid (LPA) produced by LN fibroblastic reticular cells (FRCs) acts locally to LPA2 to induce T-cell motility. In vivo, either specific ablation of LPA-producing ectoenzyme autotaxin in FRCs or LPA2 deficiency in T cells markedly decreased intranodal T cell motility, and FRC-derived LPA critically affected the LPA2-dependent T-cell motility. In vitro, LPA activated the small GTPase RhoA in T cells and limited T-cell adhesion to the underlying substrate via LPA2. The LPA-LPA2 axis also enhanced T-cell migration through narrow pores in a three-dimensional environment, in a ROCK-myosin II-dependent manner. These results strongly suggest that FRC-derived LPA serves as a cell-extrinsic factor that optimizes T-cell movement through the densely packed LN reticular network.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755752PMC
http://dx.doi.org/10.7554/eLife.10561DOI Listing

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