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

Bing Feng,Jiaqi Zhu,Qiaoling Pan,Jiong Yu,Lanjuan Li,Wenyi Chen,Hongcui Cao,Jinfeng Yang,Yanping Xu,Xinyu Sheng,Jingqi Liu,Xiaowei Shi,Xudong Feng

doi:10.1186/s13287-020-01934-x

Abstract

BackgroundImmune 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.MethodsWe 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.ResultsMSC 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.ConclusionsLung 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.

Highlights

Immune system disorders play important roles in acute lung injury (ALI), and mesenchymal stem cell (MSC) treatment can reduce inflammation during ALI
The levels of chemokines CCL3 and CCL4 were significantly decreased in the MSC-treated LPS-induced ALI model mice, but were upregulated in the LPS-only group at 3 and 7 days (Fig. 1b)
B cells are classically associated with antibody production, and we found that MSCs decreased expression of Iglc2, Iglc3, and Ighd after 7 days, while these genes were not included in the differentially expressed genes (DEGs) at 3 days after LPS and MSC treatment (Table S2)

Summary

Introduction

Immune system disorders play important roles in acute lung injury (ALI), and mesenchymal stem cell (MSC) treatment can reduce inflammation during ALI. Neutrophils play an important role in the severity and outcome of ARDS [3]. The adaptive immune system, including B cells, plays important roles in the pathogenesis of lung diseases. Randall et al reported that lung biopsies from patients with severe asthma often have B cell clusters [8]. IgM, IgG, IgE, IgA, and IgD produced by B cells are correlated with the progression of lung diseases. Cheng et al reported that IgG, IgA, and IgM are correlated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage of chronic obstructive pulmonary disease (COPD) [10]. IgG and IgA levels are increased in patients with pigeon hypersensitivity pneumonitis (HP) as well as in asymptomatic pigeon breeders [11]

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