Intestinal Lymphatics Niche Specific Properties at Homeostasis and Upon Helminth Infection

Tissue lymphatics are crucial for fluid homeostasis and immunosurveillance. We asked whether the lymphatics are adapted to the organ in which they reside, such as along the gut. Duodenal lymphatic capillaries (lacteals) displayed the most discontinuous tight junction composition within the gut, resulting in a dependence on duodenal lacteals for rapid dietary lipid uptake. Duodenal helminths abrogated these features. Parallel RNA sequencing of lymphatic endothelial cells (LECs) and mucosa along the intestine revealed that the transcriptomes overlapped in functional profiles. Helminth infection reversed key duodenal signatures like lipid metabolism and immune activation, instead triggering lymphangiogenic and mucosal antimicrobial responses. We identified a putative VEGFR-2/3 signaling gradient that may explain differences in LEC tight junctions along the small intestine at homeostasis. Inflammation-induced lymphangiogenesis likely underlay duodenal lymphatic impermeability upon helminth infection, while microbial depletion acted additively on lymphatic restructuring. Our study provides molecular insights into lymphatic function along the intestine and stages lymphatic permeability as subject to modulation by environmental queues.