Notch信号通路对变应性鼻炎肥大细胞功能影响及机制研究

Allergic rhinitis is the most common type of rhinitis, with the prevalence increased significantly over the past decade, about the impact on the global 10% -25% of the population. Previous studies have shown that there is a close relationship between the Notch signaling pathway and the immune system. Notch signaling pathway has become a hot spot of the field of medical immunology. Therefore envisaged to intervene in the signal transduction pathways before the media and cytokines released from mast cells, by cutting-off signal transfer In the more upstream parts, to avoid a series of inflammatory response in the downstream, thus the strategies to modulate some of these MC activities might be of therapeutic or prophylactic value. The project intends to investigate the role of Notch signaling in mast cell functions.Investigate the effect of mast cell activation in modulating the immune response and as the role of effector cells in the development and progression of allergic rhinitis, as well as the Notch signaling pathway in the mast cell antigen recognition, processing, presenting and effector cell function, then explore the Notch signaling pathway and activation of mast cells in the mechanism of allergic rhinitis.These new mechanisms would suggest additional drug targets to prevent the development of allergic rhinitis.If succeed, it will be a new way to more comprehensive understanding of allergic rhinitis, but also for clinical treatment and prevention.

变应性鼻炎是鼻炎中最常见的类型，近十年来其患病率明显增加，大约影响到全球10%-25%的人群。近年来研究发现，Notch信号通路与机体的免疫系统存在着密切的关系，对Notch信号通路的研究已成为了医学免疫学领域的热点。因此设想针对肥大细胞释放介质及细胞因子前的信号转导途径进行干预，在更上游部位截断信号的下传，避免产生下游的一系列炎症反应，从而从机制上更有效地防治变应性鼻炎的发作。本项目拟观察Notch信号通路对肥大细胞功能的影响，研究肥大细胞活化在变应性鼻炎发生发展过程中的调节免疫应答和作为效应细胞的作用，以及Notch信号通路调控对肥大细胞抗原识别、处理、提呈以及效应细胞功能的影响，进而探讨Notch信号通路及活化的肥大细胞在变应性鼻炎发病过程中的作用机制。以对下一步药物治疗变应性鼻炎提供靶点。如能得以成功，将为更全面地了解变应性鼻炎开辟了一条新途径，也可为临床治疗及预防提供新的思路。

变应性鼻炎是鼻炎中最常见的类型，属于I型变态反应，发病时出现连续性喷嚏、大量水样涕、鼻塞等典型症状。研究发现，肥大细胞(MC)是I型变态反应的重要细胞，激活后可通过脱颗粒释放多种生物活性物质，引起血管舒张、组织水肿、粘液分泌等效应，在变应性鼻炎中发挥关键作用。Notch信号通路不仅参与免疫系统的发育，在成熟免疫细胞的功能调节中也起着重要的作用。近期研究标明，激活骨髓来源肥大细胞(BMMC)表面的Notch受体后，此BMMC可促使CD4+T细胞偏向于Th2细胞方向。有理由推论，利用Notch信号通路调控肥大细胞的功能，能促进细胞因子释放、抗原提呈细胞形成及成熟，进一步促使变态反应的发生。本实验针对肥大细胞释放介质及细胞因子前的信号转导途径进行干预，使用DAPT成功阻断Notch信号通路及其下游分子，本实验观察到肥大细胞在抗原提呈以及作为效应细胞分泌各种活性物质的功能具有所下降，为变应性鼻炎的临床治疗及预防提供新的思路。