The lymphatic vasculature in lung function and respiratory disease

The lymphatic system is critical for maintaining lung function from birth through adulthood. In a healthy lung, lymphatic vessels are primarily located along bronchovascular structures, in interlobular septa, and in the subpleural space. These vessels perform two primary functions: they drain excess interstitial fluid to prevent edema that would otherwise impair gas exchange, and they serve as a conduit for immune surveillance. Lymphatic endothelial cells (LECs) facilitate the migration of antigen-presenting cells, such as dendritic cells, from the lung parenchyma to draining lymph nodes, where they orchestrate adaptive immune responses.

Historically, the study of pulmonary lymphatics has been hindered by their small size, thin walls, and the lack of reliable, specific imaging markers. Unlike blood vessels, lymphatic vessels are often difficult to distinguish from surrounding tissue. While modern techniques like lymphatic reporter mice and immunohistochemical staining for markers such as PROX1 and VEGFR3 have advanced the field, researchers must exercise caution. Many markers are not entirely specific to the lung lymphatic endothelium and may be expressed by other cell types, particularly in the context of lung injury or inflammation.

Recent evidence suggests that the lymphatic system is not merely a passive drainage network but an active participant in disease pathogenesis. In conditions like asthma, sarcoidosis, and chronic lung allograft dysfunction following transplantation, lymphatic remodeling is a common feature. For instance, in lung transplantation, the surgical severance of lymphatic vessels necessitates their re-establishment for graft survival. Studies indicate that promoting lymphangiogenesis can help clear inflammatory molecules and suppress rejection, highlighting the potential of the lymphatic system as a target for novel therapeutic interventions.