Dynamic Changes of NCR\u2212 Type 3 Innate Lymphoid Cells and Their Role in Mice with Bronchopulmonary Dysplasia

Jiayu Cai,Lanlan Mi,Zhengyang Xue,Hongyan Lu,Suqing Xu,Zhaoliang Su

doi:10.1007/s10753-021-01543-7

Jiayu Cai, Lanlan Mi + Show 4 more

Open Access

https://doi.org/10.1007/s10753-021-01543-7

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Abstract

—Inflammation is one of the important pathogenesis of bronchopulmonary dysplasia (BPD). Type 3 innate lymphoid cells (ILC3) play a role in a variety of inflammatory lung diseases. In this study, we established the BPD model by injecting lipopolysaccharide into the amniotic cavity of pregnant mice. Here, we investigated the dynamic changes of ILC3 and NKP46− ILC3 population in lung tissues of mice from BPD and the control groups. Results showed that the proportion of ILC3 and NKP46−ILC3 in the BPD group was higher than those of the control group. In addition, the cytokines interleukin-17 (IL-17) and interleukin-22 (IL-22) secreted by ILC3 in this model had also changed that their expression was significantly increased compared with that of the control group. Flow cytometry demonstrated that ILC3 were a rapid source of IL-17. In the anti-CD90 knockdown experiment, we confirmed the alleviation of BPD inflammation in the absence of ILC3. In addition, we injected mice with anti-IL-17 neutralizing antibody, and the results showed that IL-17 could aggravate BPD inflammation. Taken together, ILC3 may play a pro-inflammatory role in BPD by secreting IL-17.

Highlights

Bronchopulmonary dysplasia (BPD) is a chronic lung inflammatory disease that usually occurs in premature infants
Compared with the control group, the expression of N kp46+ILC3 in lung tissues of BPD group was significantly decreased (Fig. 2C, D). These results provide evidence that the ILC3 subset at work in BPD may be the population of Nkp46−ILC3
ILC3 are involved in the regulation of various inflammatory lung diseases [14,15,16,17]

Summary

Introduction

Bronchopulmonary dysplasia (BPD) is a chronic lung inflammatory disease that usually occurs in premature infants It is characterized by abnormal alveolar and pulmonary vascular development [1, 2]. Innate lymphoid cells (ILC) are a class of immune cells with adaptive immune function, which play an important role in tissue repair and homeostasis and mediate immune response in a variety of mucosal tissues [6,7,8]. They can be classified into three subsets: ILC1, ILC2, and ILC3. In intestinal inflammation, ILC3 can recruit an abundance of monocytes by secreting GM-CSF to induce inflammation and aggravate intestinal inflammation by secreting IL-17 and IFN-γ as well [15], but their role in respiratory diseases remains unclear

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