Neuromodulation of lymphatic function in intestinal Peyer's patches

ongoing

The intestine hosts a vast neuronal system, a large population of immune cells, diverse microbiota, and a complex blood and lymphatic network. The intestinal lymphatic network comprises vessels and lymphoid organs, called Peyer’s patches (PPs), that together play important roles in dietary fat absorption, mucosal immune responses and trafficking of immune cells to the rest of the body. This intestinal immune cell trafficking is key in gut-to-organ communication, and its disruption leads to immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD). PP lymphatics are major routes for B- and T-cell egress from the intestine. Yet, little is known about the specific signals that modulate lymphatic control of immune cell trafficking. This project aims to explore the novel hypothesis that a synergistic interaction between neuronal signals and PP lymphatics modulates immunity and inflammation. Building on insights from single-cell RNA sequencing of PPs, I will investigate the role of the adrenergic receptor ADRA1B in lymphatic endothelial cells. This research will focus on characterizing the molecular changes in PP lymphatic cells and elucidating patterns of immune cell egress from the gut. Also, I will examine how adrenergic signalling influences PP lymphatic function and immune cell trafficking under inflammation, mimicking IBD condition. Lastly, I will extend these findings from mouse models to humans by defining the architecture and molecular signatures of human PP endothelial cells. This multidisciplinary project will integrate high-resolution imaging, intravital microscopy, and deep molecular profiling of both mouse and human endothelial cells to uncover this previously unexplored neuronal-lymphatic-immune axis. Given the physiological relevance of PP lymphatics as major intestinal immune gatekeepers, this work will provide novel insights into gut homeostasis and open new therapeutic avenues for treating immune-mediated inflammatory diseases.