Inflammation triggers ILC3 patrolling of the intestinal barrier

Serafini and colleagues show that intestinal villus ILC3s, which are largely immotile at steady state, develop a patrolling behavior in response to inflammation. An orchestrated cellular network, including adaptive lymphocytes and group 3 innate lymphoid cells (ILC3s), maintains intestinal barrier integrity and homeostasis. T cells can monitor environmental insults through constitutive circulation, scanning tissues and forming immunological contacts, a process named immunosurveillance. In contrast, the dynamics of intestinal ILC3s are unknown. Using intravital imaging, we observed that villus ILC3s were largely immotile at steady state but acquired migratory 'patrolling' attributes and enhanced cytokine expression in response to inflammation. We showed that T cells, the chemokine CCL25 and bacterial ligands regulated intestinal ILC3 behavior and that loss of patrolling behavior by interleukin-22 (IL-22)-producing ILC3s altered the intestinal barrier through increased epithelial cell death. Collectively, we identified notable differences between the behavior of ILC3s and T cells, with a prominent adaptation of intestinal ILC3s toward mucosal immunosurveillance after inflammation.

Automated summary

Serafini and colleagues find that intestinal villus ILC3s acquire migratory 'patrolling' attributes and enhanced cytokine expression in response to inflammation. These findings reveal notable differences between ILC3s and T cells in immunosurveillance, with ILC3s showing adaptation towards mucosal immunosurveillance after inflammation.