Exosomes from adipose-derived mesenchymal stem cells alleviate sepsis-induced lung injury in mice by inhibiting the secretion of IL-27 in macrophages

Xiaoyan Wang; Danyong Liu; XiHe Zhang; LiuMing Yang; Zhengyuan Xia; Quanfu Zhang

doi:10.1038/s41420-021-00785-6

Exosomes from adipose-derived mesenchymal stem cells alleviate sepsis-induced lung injury in mice by inhibiting the secretion of IL-27 in macrophages

Cell Death Discov. 2022 Jan 10;8(1):18. doi: 10.1038/s41420-021-00785-6.

Authors

Xiaoyan Wang^#¹, Danyong Liu^#², XiHe Zhang¹, LiuMing Yang³, Zhengyuan Xia², Quanfu Zhang⁴

Affiliations

¹ Doctoral Scientific Research Center, Lianjiang People's Hospital, Zhanjiang, Guangdong, 524400, China.
² Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, China.
³ Department of Gastroenterology and Hepatology, People's Hospital of Lianjiang, Zhanjiang, Guangdong, 524400, China.
⁴ Department of Obstetrics, Shenzhen Baoan Women's and Children's Hospital, Jinan Univesity, Shenzhen, Guangdong, 518102, China. QuanfuZhang1218@163.com.

^# Contributed equally.

Abstract

Acute lung injury (ALI) represents a frequent sepsis-induced inflammatory disorder. Mesenchymal stromal cells (MSCs) elicit anti-inflammatory effects in sepsis. This study investigated the mechanism of exosomes from adipose-derived MSCs (ADMSCs) in sepsis-induced ALI. The IL-27r^-/- (WSX-1 knockout) or wild-type mouse model of sepsis was established by cecal ligation and puncture (CLP). The model mice and lipopolysaccharide (LPS)-induced macrophages were treated with ADMSC-exosomes. The content of Dil-labeled exosomes in pulmonary macrophages, macrophages CD68⁺ F4/80⁺ in whole lung tissues, and IL-27 content in macrophages were detected. The mRNA expression and protein level of IL27 subunits P28 and EBI3 in lung tissue and the levels of IL-6, TNF-α, and IL-1β were measured. The pulmonary edema, tissue injury, and pulmonary vascular leakage were measured. In vitro, macrophages internalized ADMSC-exosomes, and ADMSC-exosomes inhibited IL-27 secretion in LPS-induced macrophages. In vivo, IL-27 knockout attenuated CLP-induced ALI. ADMSC-exosomes suppressed macrophage aggregation in lung tissues and inhibited IL-27 secretion. ADMSC-exosomes decreased the contents of IL-6, TNF-α, and IL-1β, reduced pulmonary edema and pulmonary vascular leakage, and improved the survival rate of mice. Injection of recombinant IL-27 reversed the protective effect of ADMSC-exosomes on sepsis mice. Collectively, ADMSC-exosomes inhibited IL-27 secretion in macrophages and alleviated sepsis-induced ALI in mice.