Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai, 200032, China.
Inflammation. 2019 Feb;42(1):199-210. doi: 10.1007/s10753-018-0884-6.
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.
急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）与高发病率和死亡率相关。间充质干细胞（MSCs）已被证明可改善 ALI，调节性 T 细胞（Tregs）和 Th17 细胞的失衡与 ALI/ARDS 患者的死亡率相关。然而，肺驻留间充质干细胞（LRMSC）的给药是否改善肺损伤并调节 Tregs 和 Th17 细胞的平衡尚不清楚。通过 LPS 诱导 ALI 动物模型，在 4 小时后通过尾静脉给予 PBS 或 LRMSC。随后通过活体成像系统（Berthold LB983，德国）检测肺中的 LRMSC。检测肺形态；肺湿重/干重比；以及支气管肺泡灌洗液（BALF）和血浆中的总蛋白浓度、炎症细胞和细胞因子。还评估了肺和脾中的 Tregs 百分比，以及肺和血液中的 Th17 细胞百分比。结果表明，LRMSC 不仅减轻了组织病理学损伤，还介导了肺湿重/干重比的下调以及 BALF 中总蛋白浓度和炎症细胞的减少。LRMSC 还降低了 BALF 和血浆中的炎症细胞因子，并增加了肺中的 KGF-2 和表面活性蛋白 C（SPC）表达。流式细胞术显示 Tregs 的上调和 Th17 细胞的下调，以及 Tregs 和 Th17 细胞的比值增加。活体成像系统显示 LRMSC 迁移到并保留在损伤区域。总之，这些结果表明，LRMSC 的给药通过上调 Tregs 和 Th17 细胞的平衡来减轻 LPS 诱导的 ALI。
