Extended Data Fig. 8: Monitoring of intestinal tissue by patrolling ILC3s.

The intestinal mucosa is continuously exposed to environmental stimuli that can induce immune responses through adaptation of local immune cells, including ILC3s. Under basal conditions, villus T cells control ILC3 patrolling though competition for the chemokine CCL25, and consequently villus ILC3s are largely immotile. Disruption of intestinal homeostasis, notably during TLR5-mediated inflammation, leads to the activation of ILC3s and to CCL25-mediated ILC3 patrolling of the intestinal barrier. Intestinal ILC3s produce IL-22 which is critical to prevent IEC death and to maintain the integrity of the intestinal barrier. Tissue scanning of patrolling ILC3s within intestinal villi could be important to support elevated IL-22 concentrations close to IECs and for optimal induction of their functional programs in order to maintain intestinal integrity. Collectively, tissue environmental signals shape intestinal ILC3 activity, including patrolling behavior and IL-22 production, to promote appropriate immune responses and intestinal barrier function. ILC3, group 3 innate lymphoid cell; DC, dendritic cell. CCL25, chemokine ligand 25; TLR-5, Toll-like receptor 5; IL-22, interleukin 22; IEC, intestinal epithelial cell.