Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality. Mesenchymal stem cells (MSCs) have been shown to improve ALI, and the imbalance of regulatory T cells (Tregs) and Th17 cells is associated with mortality in ALI/ARDS patients. However, whether administration of lung-resident MSC (LRMSC) improves lung injury and regulates the balance of Tregs and Th17 cells remains unknown. An ALI animal model was induced by LPS, and PBS or LRMSC were administered via tail vein after 4 h. LRMSC were subsequently detected in the lungs by a live imaging system (Berthold LB983, Germany). Lung morphology; lung wet-to-dry weight ratio; and total protein concentration, inflammatory cells, and cytokines in bronchoalveolar lavage fluid (BALF) and plasma were determined. The percentage of Tregs in lung and spleen, and of Th17 cells in lung and blood, were also evaluated. The results showed that LRMSC not only attenuated histopathological damage but also mediated the downregulation of lung wet-to-dry weight ratio and the reduction of total protein concentration and inflammatory cells in BALF. LRMSC also decreased inflammatory cytokines in both BALF and plasma and increased KGF-2 and surfactant protein C (SPC) expression in the lung. Flow cytometry revealed the upregulation of Tregs and the downregulation of Th17 cells, and the increase in the ratio of Tregs and Th17 cells. The live imaging system showed that LRMSC migrated to and were retained in the injured area. In conclusion, the results indicated that administration of LRMSC attenuates LPS-induced ALI via upregulating the balance of Tregs and Th17 cells.
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Funding
This study was supported by The National Natural Science Foundation of China key grant (81630001, 81490533) and grant (81770075, 81500026, 81570028, 81600056, 81870062), The State Key Basic Research Program project (2015CB553404), Shanghai Science and Technology Committee grant (15DZ1930600/15DZ1930602/16ZR1405700, 18140-903400) and Shanghai Municipal Commission of Health and Family Planning (201540370), Shanghai Science and Technology Committee Grant (15DZ1941103), Fudan University (IAH6281420/058).
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Linlin Wang performed the experiments, analyzed the data, and wrote the manuscript. Meng Shi, Xiaocen Wang, Jian Wang, Shimeng Ji, Jing Bi, Cuicui Chen, Lin Tong, and Dong Yang analyzed the data. Yuanlin Song, Jian Zhou, and Chunxue Bai designed the study and wrote and revised the manuscript. All the authors read and approved the final manuscript.
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Linlin Wang and Meng Shi are Co-first authors.
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Wang, L., Shi, M., Tong, L. et al. Lung-Resident Mesenchymal Stem Cells Promote Repair of LPS-Induced Acute Lung Injury via Regulating the Balance of Regulatory T cells and Th17 cells. Inflammation 42, 199–210 (2019). https://doi.org/10.1007/s10753-018-0884-6
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DOI: https://doi.org/10.1007/s10753-018-0884-6