维持促炎和抗炎反应平衡是ALI治疗的关键环节。MSC能免疫调控ALI失衡的炎症反应，但具体机制尚不清楚。课题组前期及国外研究显示，Th17/Tregs失衡在ALI炎症反应失衡中发挥重要作用，MSC能调节Th17/Tregs极化平衡，而HGF/c-Met通路是MSC发挥炎症调节的重要信号通路。因此提出假设：MSC通过激活HGF/c-Met信号通路调节ALI时Th17/Tregs平衡，继而调控ALI失衡的炎症反应。本项目首先明确MSC在调节ALI时Th17/Tregs平衡中的作用；然后体外实验在MSC与初始性CD4+T细胞共培养的基础上，干扰MSC表达HGF，证实HGF/c-Met信号通路在MSC调节Th17/Tregs平衡中的重要作用；最后构建高表达HGF的MSC，研究其对ALI小鼠Th17/Tregs平衡及肺损伤修复的影响，为优化ALI的干细胞治疗提供理论依据。

Maintaining the balance between pro-inflammatory and anti-inflammatory is the key treatment target for acute lung injury (ALI).As a promising treatment for ALI, mesenchymal stem cells (MSCs) have been confirmed recently effectively to inhibit the inflammaiton, however, the detailed mechanisms are still unclear. Studies show that Th17/Tregs imbalance of CD4+ T cells plays great effect in mediating ALI inflammatory injury.It was reported that MSCs are capable of regulating the balance between pro-inflammatory and anti-inflammatory. Our previous studies indicated that MSCs regulate the balance between pro-inflammatory and anti-inflammatory in ALI mainly through HGF/c-Met pathway.Therefore, we hypothesized that MSCs promote CD4+ T differentiation from Th17 to Tregs by HGF/c-Met pathway thereby ameliorating the pulmonary impairment.In this study, we would investigate the role of MSCs in regulating the balance of Th17/Tregs in vitro. Moreover, based on MSCs co-cultured with native CD4+ T cells, the expression of HGF mRNA was interfered, thus to verify the vital role of HGF/c-Met pathway in regulating the balance of Th17/Tregs. At last, we will study the effect of MSCs with the high expression of HGF on the balance of Th17/Tregs and the role of lung injury repair. In this way, the study may contribute to MSCs with optimal treatment to ALI.