间充质干细胞通过调节Treg/Th17平衡治疗哮喘作用机制研究

Asthma has been recognized as a disease of dysregulated immunity characterized by chronic airway inflammation and remodeling. Although the Th1/Th2 imbalance likely plays an important role in allergic asthma, there are shortcomings to the notion that Th2 inflammation is the only mechanism involved in asthma.Recently,regulatory T cells (Treg cells) and T-helper17 (Th17) cells have been described as two distinct subsets from Th1 and Th2 cells that play relevant roles in vivo. The equilibrium between Treg and Th17 is extensively deliberated in.allergic diseases including asthma, and imbalance in Th17/Treg is postulated to be an important component in the allergic airway inflammation in asthma. Mesenchymal stem cells (MSCs) are emerging as a therapeutic modality in various inflammatory and autoimmune diseases.Recent studies demonstrated that MSCs could influence differentiation of Th17 cells and Tregs, and in this way to modulate.autoimmune,immunopathological,and protective immunereactions. Herein, we sought to investigate whether MSCs exert an anti-inflammatory effect via regulation of Foxp3+Treg/Th17 balance in ovalbumin-sensitized mice,and the Notch pathway were studied.

既往研究认为 Th1/Th2 细胞的平衡理论是哮喘发病的核心，但Th1/Th2 细胞的平衡理论并不能解释哮喘发生的所有现象。近期研究发现T淋巴细胞新亚群—调节性T细胞及Th17细胞(Treg/Th17)失衡在哮喘的发病中起着重要作用。间充质干细胞(MSCs)作为一种新型的种子细胞，因其强大的免疫调节活性广泛应用于多种炎症性疾病及自身免疫性疾病中，多项研究发现MSCs能上调Treg功能及抑制Th17活化，因此我们假设MSCs能够通过调节Treg/Th17平衡在哮喘的治疗中发挥作用，因此我们以BALB/c小鼠建立哮喘模型，观察：(1)MSCs对哮喘小鼠气道炎症及气道重塑的影响(2)MSCs对哮喘小鼠肺组织及脾脏Treg、Th17百分比及细胞因子分泌的影响；(3)观察Notch信号通路在此所发挥的作用。