Aquaporin-1 sustains lymphangiogenic responses in inflammatory microenvironments

Specialized villus lymphatic capillaries, lacteals, undergo constant VEGF-C-dependent renewal to maintain their function in a high-osmolarity, inflammatory microenvironment exposed to dietary by-products. The mechanisms of lacteal adaptation remain incompletely understood.

We integrated new and published single-cell RNA-sequencing data to profile murine small-intestinal lymphatic endothelial cells (LECs) and identified three distinct subsets. Lacteal LECs display a transcriptional signature resembling Ptx3⁺ immune-interacting LECs characterized by high expression of Aqp1, encoding the aquaporin-1 water channel. LEC-specific deletion of Aqp1 reduced lacteal length, impaired lipid uptake, and limited weight gain on a high-fat diet, underscoring the importance of water homeostasis in lacteal maintenance.