Lung-Resident Mesenchymal Stem Cells Promote Repair of LPS-Induced Acute Lung Injury via Regulating the Balance of Regulatory T cells and Th17 cells
Lung-Resident Mesenchymal Stem Cells Promote Repair of LPS-Induced Acute Lung Injury via Regulating the Balance of Regulatory T cells and Th17 cells
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肺驻留间充质干细胞通过调节调节性 T 细胞和 Th17 细胞的平衡促进 LPS 诱导的急性肺损伤的修复
DOI：
10.1007/s10753-018-0884-6
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发表时间：
2018
期刊：
影响因子：
5.1
通讯作者：
Yuanlin Song
中科院分区：
文献类型：
--
作者：
Linlin Wang;Meng Shi;Lin Tong;Jian Wang;Shimeng Ji;Jing Bi;Cuicui Chen;Jinjun Jiang;Chunxue Bai;Jian Zhou;Yuanlin Song
急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)具有较高的发病率和死亡率。间充质干细胞(MSCs)可改善ALI，调节性T细胞(Tregs)和Th17细胞的失衡与ALI/ARDS患者的死亡率有关。然而，肺常驻MSC(LRMSC)是否能改善肺损伤并调节Tregs/Th17细胞的平衡仍不清楚。用脂多糖诱导大鼠ALI模型，4h后尾静脉注射PBS或LRMSC，活体成像系统检测肺组织中的LRMSC。测定肺组织形态、肺湿干重比、总蛋白浓度、肺泡灌洗液(BALF)和血浆中炎症细胞及细胞因子的含量。测定肺、脾组织中Tregs细胞百分率及肺、外周血中Th17细胞百分率。结果表明，LRMSC不仅能减轻肺组织病理损伤，而且能降低肺湿/干质量比，降低BALF中总蛋白浓度和炎性细胞数。LRMSC还可降低BALF和血浆中的炎性细胞因子，增加肺组织KGF-2和表面活性蛋白C(SPC)的表达。流式细胞仪检测发现Tregs表达上调，Th17细胞表达下调，Tregs/Th17细胞比例升高。活体成像系统显示LRMSC迁移至损伤区并保留在损伤区。综上所述，LRMSC可通过上调Tregs/Th17细胞的平衡来减轻内毒素诱导的ALI。
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.