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Published on: December 16, 2013
Clonal Proliferation and Stochastic Pruning Orchestrate Lymph Node Vasculature Remodeling
Isabelle Mondor1, Audrey Jorquera1, Cynthia Sene1
1Aix-Marseille Université, CNRS, INSERM, CIML, 13288 Marseille, France.
Insights
Lymph node vasculature expands via sequential assembly of endothelial cell units, driven by high endothelial venule cells. Vascular contraction involves cell death, revealing immune response dynamics.
Area of Science:
- Immunology
- Vascular Biology
- Cell Biology
Background:
- Lymph node (LN) expansion during immune responses involves vascular remodeling.
- Mechanisms of LN endothelial cell division are partially understood, but single-cell dynamics remain unclear.
Purpose of the Study:
- To comprehensively map LN endothelial cell dynamics at the single-cell level during immune responses.
- To elucidate the mechanisms of vascular expansion and contraction in lymph nodes.
Main Methods:
- Utilized multicolored fluorescent fate-mapping models.
- Tracked blood endothelial cell behavior during LN expansion and return to homeostasis.
Main Results:
- LN vascular expansion occurs through sequential assembly of endothelial cell proliferative units.
- High endothelial venule (HEV) cells act as progenitors, driving clonal proliferation for new vessels.
- Vascular contraction involves stochastic death of both existing and newly formed endothelial cells.
Conclusions:
- Single-cell fate mapping reveals complex dynamics of vascular remodeling in lymph nodes.
- Identified HEV cells as key progenitors in LN vascular expansion.
- Demonstrated the role of cell death in LN vascular homeostasis following immune response.
Abstract:
Lymph node (LN) expansion during an immune response relies on the transient remodeling of its vasculature. Although the mechanisms driving LN endothelial cell division are beginning to be understood, a comprehensive view of LN endothelial cell dynamics at the single-cell level is lacking. Here, we used multicolored fluorescent fate-mapping models to track the behavior of blood endothelial cells during LN expansion upon inflammation and subsequent return to homeostasis. We found that expansion of the LN vasculature relied on the sequential assembly of endothelial cell proliferative units. This segmented growth was sustained by the clonal proliferation of high endothelial venule (HEV) cells, which act as local progenitors to create capillaries and HEV neo-vessels at the periphery of the LN. Return to homeostasis was accompanied by the stochastic death of pre-existing and neo-synthesized LN endothelial cells. Thus, our fate-mapping studies unravel-at a single-cell level-the complex dynamics of vascular-tree remodeling during LN expansion and contraction.
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