Gut lymphatics functionally adapt to the region they drain and are altered by helminths [NI-Sv_5-8_dpi_Mucosa_RNAseq]

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 mot discontinuous tight junction composition versus lacteals at other sites, resulting in a dependence on duodenal lacteals for rapid dietary lipid uptake. Duodenal helminths abrogated these features. RNAseq of LECs and the mucosa along the intestine revealed that LEC transcriptomes matched the functional profile of the local mucosa. Helminth infection reverses key duodenal signatures like lipid metabolism and immune activation, instead triggering lymphangiogenic and mucosal antimicrobial responses. We identified a putative VEGFR2/3 signaling gradient that may explain differences in tight junction along the small intestine at homeostasis. Inflammation-induced lymphangiogenesis and decreased fat exposure likely underlie 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 dynamic regulation by environmental queues.