Ontogeny of ROR\u03b3t+ cells in the intestine of newborns and its role in the development of experimental necrotizing enterocolitis

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

doi:10.1186/s13578-021-00739-6

Abstract

BackgroundNeonates 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.ResultsWe 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.ConclusionsOur data reveal the high proportion of RORγt+ cells in newborn mice may directly contribute to the development of NEC.

Highlights

Neonates possess an immature and plastic immune system, which is a major cause of some diseases in newborns
Ontogeny of receptor γt (RORγt)+ cells in intestinal lamina propria of neonatal mice The ontogeny of intestinal immune cells was investigated in normal neonatal mice to seek causes leading to intestinal disease in early life
**p < 0.01; ***p < 0.001; ****p < 0.0001 our previous results, we considered whether the RORγt antagonist could inhibit IL-17A expressed to prevent the development of Necrotizing enterocolitis (NEC) in mice

Summary

Introduction

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. The development of intestinal immune cells in neonates and their roles in the pathological process of NEC have not been elucidated. Necrotizing enterocolitis (NEC) is a life-threatening disease that affects approximately 7% of infants with a birth weight under 1500 g [1]. Zhao et al Cell & Bioscience (2022) 12:3 and very low birth weight infants, the intestinal barrier and immune system are immature, which predispose them to have risk of subjecting to late-on sepsis or NEC [11]. The excessive activation of TLR4 by lipopolysaccharide (LPS) leads to an infiltration of CD4+ T lymphocytes, and predispose the populations to pro-inflammatory type 17 T helper (Th17) cells, which is required for the development of NEC [15]. The excessive inflammatory response triggers the vicious cycle that exacerbates tissue injury and necrosis of intestine, resulting in NEC development [19]

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