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

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

doi:10.1186/s13578-021-00739-6

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

Cell Biosci. 2022 Jan 4;12(1):3. doi: 10.1186/s13578-021-00739-6.

Authors

Xiuhao Zhao^#^{1

2

3}, Wenhua Liang^#³, Yonghui Wang⁴, Ruirong Yi³, Lingjie Luo³, Weifang Wang³, Nannan Sun⁴, Mingcheng Yu⁴, Weijue Xu², Qingfeng Sheng², Li Lu², Jianfeng Pang³, Zhibao Lv^{5

6}, Feng Wang^{7

8}

Affiliations

¹ Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
² Department of General Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, 355 Luding Road, Putuo, Shanghai, China.
³ Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, China.
⁵ Department of General Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, 355 Luding Road, Putuo, Shanghai, China. zhibaolyu@163.com.
⁶ Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhibaolyu@163.com.
⁷ Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wangfeng16@sjtu.edu.cn.
⁸ Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, 280 South of Chongqing Road, Huangpu, Shanghai, China. wangfeng16@sjtu.edu.cn.

^# Contributed equally.

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.

Keywords: Intestinal immune; Necrotizing enterocolitis; Neonate; RORγt.

Abstract

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