IL-2 in vascular biology

IL-2 receptor expression on smooth muscle cells in human iliac artery. Scale bar = 10 µm.

How does monomeric IL-2 impact vascular smooth muscle cell function?

Smooth muscle cells express IL-2 receptors, yet no one knows how IL-2 impacts the function of smooth muscle cells. Our lab has shown, however, that IL-2 deficient mice lose smooth muscle cells over time, leading to aortic aneurysms and esophageal ectasia (widening). This project addresses whether IL-2 impacts proliferation, survival, migration, and other "behaviors" of smooth muscle cells.

How do multimeric forms of IL-2 impact vascular smooth muscle cell function?

IL-2 tends to self-associate and form multimers. In the mid-90's, the Schwartz lab discovered that a dimeric form of IL-2 was cytotoxic to oligodendrocytes. Since then we have shown that the dimeric form of IL-2 is cytotoxic to smooth muscle cells, epithelial cells, T cells, and any cells (to date) that have an IL-2 receptor. This project addresses how dimeric IL-2 kills smooth muscle and other susceptible cells. In addition, we are also addressing conditions that predispose to dimer formation.

IL-2 is cytotoxic to kidney epithelial cells.

How does IL-2 impact vascular pathology such as atherosclerosis?

IL-2 is present in blood vessels through binding to the extracellular matrix. The projects above feed into the bigger question, "What does IL-2 in a blood vessel do?" How do diseases such as atherosclerosis impact the level and forms of IL-2? Do differences in the amounts or forms of IL-2 initiate or propagate disease? This project is designed to address these questions.