Regulation of lymphatic permeability

The lymphatic vascular system is our second vascular system that returns extravasated fluid and macromolecules to the blood circulation, in addition to immune cell trafficking and intestinal fat absorption. The lymphatic vascular system is organized into lymphatic capillaries and lymphatic collectors. While lymphatic endothelial cells (LECs) in capillaries are connected via discontinuous junctions reminiscent of ‘buttons’, LECs in collectors are connected via continuous junctions reminiscent of ‘zippers’. We have shown that button junctions in intestinal lymphatic capillaries are required for lipid absorption, and that mice with zippered intestinal capillaries do not gain weight when put on a high fat diet. Central to this button to zipper transformation is the activity of VEGFR2, a receptor mainly known for its function in blood endothelial cells. We are now studying the upstream regulators and downstream signaling pathways controlling button morphology not only in the intestine, but also in other tissues. We are also investigating the role of buttons in other functions of the lymphatic vasculature, such as tissue drainage.

  • Lymphatic junction heterogeneity

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