Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury
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RESEARCH
Open Access
Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury Bing Feng1,2, Jiaqi Zhu1,2, Yanping Xu1,2, Wenyi Chen1,2, Xinyu Sheng1,2, Xudong Feng1,2, Xiaowei Shi1, Jingqi Liu1, Qiaoling Pan1,2, Jinfeng Yang1,2, Jiong Yu1,2, Lanjuan Li1,2 and Hongcui Cao1,2,3*
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. Keywords: Mesenchymal stem cells, Lung B cells, Single-cell RNA sequencing, Acute lung injury * Correspondence: [email protected] 1 State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou City 310003, China 2 National Clinical Research Center for Infectious Diseases, 79 Qingchun Rd, Hangzhou City 310003, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the or
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