Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury

Abstract Background Immune system disorders play important roles in acute lung injury (ALI), and mesenchymal stem cell (MSC) treatment can reduce inflammation during ALI. In this study, we compared the changes in lung B cells during MSC treatment. Methods We investigated the effects of MSCs on lung...

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Main Authors: Bing Feng, Jiaqi Zhu, Yanping Xu, Wenyi Chen, Xinyu Sheng, Xudong Feng, Xiaowei Shi, Jingqi Liu, Qiaoling Pan, Jinfeng Yang, Jiong Yu, Lanjuan Li, Hongcui Cao
Format: Article
Language:English
Published: BMC 2020-09-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13287-020-01934-x
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author Bing Feng
Jiaqi Zhu
Yanping Xu
Wenyi Chen
Xinyu Sheng
Xudong Feng
Xiaowei Shi
Jingqi Liu
Qiaoling Pan
Jinfeng Yang
Jiong Yu
Lanjuan Li
Hongcui Cao
author_facet Bing Feng
Jiaqi Zhu
Yanping Xu
Wenyi Chen
Xinyu Sheng
Xudong Feng
Xiaowei Shi
Jingqi Liu
Qiaoling Pan
Jinfeng Yang
Jiong Yu
Lanjuan Li
Hongcui Cao
author_sort Bing Feng
collection DOAJ
description Abstract Background Immune system disorders play important roles in acute lung injury (ALI), and mesenchymal stem cell (MSC) treatment can reduce inflammation during ALI. In this study, we compared the changes in lung B cells during MSC treatment. Methods We investigated the effects of MSCs on lung B cells in a mouse model of lipopolysaccharide (LPS)-induced ALI. MSCs were administered intratracheally 4 h after LPS. As vehicle-treated controls, mice were treated with phosphate-buffered saline (PBS) containing 2% C57BL/6 (PBS group). Histopathological changes, survival rate, inflammatory factor levels, and the number of neutrophils in bronchoalveolar lavage fluid (BALF) were determined. Single-cell RNA sequencing (scRNA-Seq) analysis was performed to evaluate the transcriptional changes in lung B cells between the PBS, LPS, and LPS/MSC groups on days 3 and 7. Results MSC treatment ameliorated LPS-induced ALI, as indicated by the reductions in mortality, the levels of chemokines and cytokines in BALF, and the severity of lung tissue histopathology in ALI mice. Lung B cells in the PBS group remained undifferentiated and had an inhibitory phenotype. Based on our scRNA-Seq results, the differentially expressed genes (DEGs) in lung B cells in both the PBS group and LPS group were involved in chemotaxis processes and some proinflammatory pathways. MSC treatment inhibited the expression of chemokine genes that were upregulated by LPS and were related to the recruitment of neutrophils into lung tissues. Immunoglobulin-related gene expression was decreased in lung B cells of mice treated with LPS/MSC for 7 days. The DEGs regulated by MSCs were enriched in biological processes, including humoral immune response and apoptotic signaling. Conclusions Lung B cells played an important role in the effects of treatment of ALI with MSCs. These observations provide new insights into the mechanisms underlying the effects of MSC treatment for ALI.
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spelling doaj.art-7c4085476baf41c59a0d05631fb888202022-12-22T02:44:28ZengBMCStem Cell Research & Therapy1757-65122020-09-011111910.1186/s13287-020-01934-xImmunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injuryBing Feng0Jiaqi Zhu1Yanping Xu2Wenyi Chen3Xinyu Sheng4Xudong Feng5Xiaowei Shi6Jingqi Liu7Qiaoling Pan8Jinfeng Yang9Jiong Yu10Lanjuan Li11Hongcui Cao12State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityAbstract Background Immune system disorders play important roles in acute lung injury (ALI), and mesenchymal stem cell (MSC) treatment can reduce inflammation during ALI. In this study, we compared the changes in lung B cells during MSC treatment. Methods We investigated the effects of MSCs on lung B cells in a mouse model of lipopolysaccharide (LPS)-induced ALI. MSCs were administered intratracheally 4 h after LPS. As vehicle-treated controls, mice were treated with phosphate-buffered saline (PBS) containing 2% C57BL/6 (PBS group). Histopathological changes, survival rate, inflammatory factor levels, and the number of neutrophils in bronchoalveolar lavage fluid (BALF) were determined. Single-cell RNA sequencing (scRNA-Seq) analysis was performed to evaluate the transcriptional changes in lung B cells between the PBS, LPS, and LPS/MSC groups on days 3 and 7. Results MSC treatment ameliorated LPS-induced ALI, as indicated by the reductions in mortality, the levels of chemokines and cytokines in BALF, and the severity of lung tissue histopathology in ALI mice. Lung B cells in the PBS group remained undifferentiated and had an inhibitory phenotype. Based on our scRNA-Seq results, the differentially expressed genes (DEGs) in lung B cells in both the PBS group and LPS group were involved in chemotaxis processes and some proinflammatory pathways. MSC treatment inhibited the expression of chemokine genes that were upregulated by LPS and were related to the recruitment of neutrophils into lung tissues. Immunoglobulin-related gene expression was decreased in lung B cells of mice treated with LPS/MSC for 7 days. The DEGs regulated by MSCs were enriched in biological processes, including humoral immune response and apoptotic signaling. Conclusions Lung B cells played an important role in the effects of treatment of ALI with MSCs. These observations provide new insights into the mechanisms underlying the effects of MSC treatment for ALI.http://link.springer.com/article/10.1186/s13287-020-01934-xMesenchymal stem cellsLung B cellsSingle-cell RNA sequencingAcute lung injury
spellingShingle Bing Feng
Jiaqi Zhu
Yanping Xu
Wenyi Chen
Xinyu Sheng
Xudong Feng
Xiaowei Shi
Jingqi Liu
Qiaoling Pan
Jinfeng Yang
Jiong Yu
Lanjuan Li
Hongcui Cao
Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury
Stem Cell Research & Therapy
Mesenchymal stem cells
Lung B cells
Single-cell RNA sequencing
Acute lung injury
title Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury
title_full Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury
title_fullStr Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury
title_full_unstemmed Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury
title_short Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury
title_sort immunosuppressive effects of mesenchymal stem cells on lung b cell gene expression in lps induced acute lung injury
topic Mesenchymal stem cells
Lung B cells
Single-cell RNA sequencing
Acute lung injury
url http://link.springer.com/article/10.1186/s13287-020-01934-x
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