Ontogeny of RORγt+ cells in the intestine of newborns and its role in the development of experimental necrotizing enterocolitis

Author:

Zhao Xiuhao,Liang Wenhua,Wang Yonghui,Yi Ruirong,Luo Lingjie,Wang Weifang,Sun Nannan,Yu Mingcheng,Xu Weijue,Sheng Qingfeng,Lu Li,Pang Jianfeng,Lv ZhibaoORCID,Wang Feng

Abstract

Abstract Background 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. Results We examined the ontogeny of intestinal lamina propria lymphocytes in the early life of mice and found a high percentage of RORγt+ cells (containing inflammatory Th17 and ILC3 populations) during the first week of life. Importantly, the proportion of RORγt+ 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 RORγt, inhibited IL-17A release and ameliorated NEC severity. Conclusions Our data reveal the high proportion of RORγt+ cells in newborn mice may directly contribute to the development of NEC.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Top Young Talent Program of Shanghai, and the Technology Committee of Shanghai Municipality

Publisher

Springer Science and Business Media LLC

Subject

General Biochemistry, Genetics and Molecular Biology

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