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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BMC
2020-09-01
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Series: | Stem Cell Research & Therapy |
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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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language | English |
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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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