Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury

The intestinal epithelium undergoes continuous renewal and has an exceptional capacity to regenerate after injury. Maintenance and proliferation of intestinal stem cells (ISCs) are regulated by their surrounding niche, largely through Wnt signaling. However, it remains unclear which niche cells produce signals during different injury states, and the role of endothelial cells (ECs) as a component of the ISC niche during homeostasis and after injury has been underappreciated. Here, we show that lymphatic endothelial cells (LECs) reside in prox-imity to crypt epithelial cells and secrete molecules that support epithelial renewal and repair. LECs are an essential source of Wnt signaling in the small intestine, as loss of LEC-derived Rspo3 leads to a lower number of stem and progenitor cells and hinders recovery after cytotoxic injury. Together, our findings identify LECs as an essential niche component for optimal intestinal recovery after cytotoxic injury.

Automated summary

The intestinal epithelium can continuously renew and regenerate, and the proliferation and maintenance of intestinal stem cells (ISCs) are regulated by their surrounding niche cells. In this study, lymphatic endothelial cells (LECs) were found to play an essential role in supporting epithelial renewal and repair by secreting molecules in close proximity to crypt epithelial cells. LECs were identified as a crucial source of Wnt signaling in the small intestine, and their loss hindered recovery after cytotoxic injury.