Ontogeny of ROR[gamma]t+ cells in the intestine of newborns and its role in the development of experimental necrotizing enterocolitis

Neonates possess an immature and plastic immune system, which is a major cause of some diseases in newborns. Necrotizing enterocolitis (NEC) is a severe and devastating intestinal disease that typically affects premature infants. However, the development of intestinal immune cells in neonates and their roles in the pathological process of NEC have not been elucidated. We examined the ontogeny of intestinal lamina propria lymphocytes in the early life of mice and found a high percentage of ROR[gamma]t.sup.+ cells (containing inflammatory Th17 and ILC3 populations) during the first week of life. Importantly, the proportion of ROR[gamma]t.sup.+ cells of intestinal lamina propria further increased in both NEC mice and patients tissue than the control. Furthermore, the application of GSK805, a specific antagonist of ROR[gamma]t, inhibited IL-17A release and ameliorated NEC severity. Our data reveal the high proportion of ROR[gamma]t.sup.+ cells in newborn mice may directly contribute to the development of NEC.