New R01: Biology of Lymphangiogenesis in the Adult Lung

In June, we were delighted to learn that our new R01 entitled Biology of Lymphangiogenesis in the Adult Lung was funded. This work builds upon exciting data generated by Senegal Carty (PiBS graduate student) and Erin Crossey MD, PhD (pulmonary fellow; Figure 1) demonstrating that robust lymphangiogenesis (Figure 2) and changes in lymphatic cell phenotype accompany influenza infection of the lung.

Senegal Carty
Erin Crossey MD, PhD

From a historical point-of-view, it has long been known that the lung’s lymphatic system is required for the maintenance of normal lung function as a result of its central role in maintaining fluid homeostasis and by serving as a conduit for immune cell trafficking. Located at peri-bronchial, peri-vascular and distal lung sites, and lined by specialized endothelial cells (LECs), a more expansive role for this network in the lung’s host response to infection has been proposed. Indeed, there is a nascent literature that implicates LECs as direct immune cell regulators.

Figure 2: Influenza infection of the adult mouse lung induces lymphangiogenesis. PROX1 (LEC transcription factor) positive nuclei were quantified in tissue sections collected from mice exposed to saline (n=4) or flu (n=3) for 21 days (****p<0.0001; left). Representative tissue sections from saline (middle) or flu-infected mice (right) are shown. PROX1 positive LECs stain brown.

While further ascertaining the role of LECs in immune regulation is one key question, there remain other significant questions regarding the basic biology of LECs. For example, whether there are functionally and/or anatomically distinct subtypes of LECs in normal and diseased tissues, including the lung is not clear. In addition, there is little information regarding the origin of new adult lung LECs and the mechanism of their expansion. In sum, the overall goal of our R01 is to extend our preliminary data by utilizing tools and technologies we developed to resolve fundamental questions in lung LEC biology.