2025-06-18 バージニア工科大学(VirginiaTech)
Virginia Tech researcher Jennifer Munson’s bioengineered stromal cells — which include fibroblastic reticular (at left) and endothelial cells (at right) — are the framework within a lymph node that provide structure, guide immune cell movement, and can influence the immune response. Image courtesy of the Munson Lab.
<関連情報>
- https://news.vt.edu/articles/2025/06/research_fralinbiomed_munsonchip_0611.html
- https://pubs.aip.org/aip/apb/article/9/2/026105/3342507/Interstitial-fluid-flow-in-an-engineered-human
人工ヒトリンパ節間質モデルにおける間質液の流れがT細胞の脱出と間質の変化を調節する
Interstitial fluid flow in an engineered human lymph node stroma model modulates T cell egress and stromal change
Jennifer H. Hammel;Abhinav Arneja;Jessica Cunningham;Maosen Wang;Sophia Schumaecker;Yamilet Macias Orihuela;Tochukwu Ozulumba;Jonathan M. Zatorski;Thomas J. Braciale;Chance John Luckey;Rebecca R. Pompano;Jennifer M. Munson
APL Bioengineering Published:April 04 2025
DOI:https://doi.org/10.1063/5.0247363
The lymph node (LN) performs essential roles in immunosurveillance throughout the body. Developing in vitro models of this key tissue is of great importance to enhancing physiological relevance in immunoengineering. The LN consists of stromal populations and immune cells, which are highly organized and bathed in constant interstitial fluid flow (IFF). The stroma, notably the fibroblastic reticular cells (FRCs) and the lymphatic endothelial cells (LECs), play crucial roles in guiding T cell migration and are known to be sensitive to fluid flow. During inflammation, interstitial fluid flow rates drastically increase in the LN. It is unknown how these altered flow rates impact crosstalk and cell behavior in the LN, and most existing in vitro models focus on the interactions between T cells, B cells, and dendritic cells rather than with the stroma. To address this gap, we developed a human engineered model of the LN stroma consisting of FRC-laden hydrogel above a monolayer of LECs in a tissue culture insert with gravity-driven interstitial flow. We found that FRCs had enhanced coverage and proliferation in response to high flow rates, while LECs experienced decreased barrier integrity. We added CD4+ and CD8+ T cells and found that their egress was significantly decreased in the presence of interstitial flow, regardless of magnitude. Interestingly, 3.0 μm/s flow, but not 0.8 μm/s flow, correlated with enhanced inflammatory cytokine secretion in the LN stroma. Overall, we demonstrate that interstitial flow is an essential consideration in the lymph node for modulating LN stroma morphology, T cell migration, and inflammation.
