Sirt1通过Notch通路调节Th22细胞功能在白塞氏病中的作用机制研究

Behcet’s disease is one of the most common uveitis entities leading to blindness in China. Abnormal activated IL-22-producing T helper cells 22 (Th22 cells) mediated inflammatory response is accepted as the one of the vital mechanisms involved in Behcet’s disease. Sirt1, has an effect on the maturation and differentiation of T cells, and exerts immune-regulatory role via down-regulation of Notch pathway in several autoimmune diseases. Our recent study found a significantly decreased expression of Sirt1, in association with excessive activation of Notch pathway, and with increased expression of IL-22 in patients with active Behcet’s disease. Further study showed inhibition of Notch pathway could suppress the secretion of IL-22 by CD4+ T cells. These results suggest that Sirt1 might involve in Behcet’s disease. Our study will focus on the role of Sirt1 in Behcet's disease via Notch pathway-mediated regulation of Th22 cells. We hope to clarify the role and mechanisms of Sirt1 in the development of Behcet’s disease, and this study may offer a new molecular biomarker and therapeutic approach for patients with Behcet’s disease.

白塞氏病是我国最常见的致盲性葡萄膜炎类型之一，最新研究表明异常活化的辅助性T细胞22（Th22细胞，以分泌IL-22为主要特征）可介导皮肤黏膜的炎症反应，是白塞氏病的重要发病机制之一。Sirt1可影响T细胞的成熟、分化，且能通过下调Notch通路在自身免疫性疾病中起免疫调节作用。我们预实验发现：在活动期白塞氏病患者中Sirt1表达显著降低，并伴有Notch通路的高度激活，以及IL-22的高表达，同时抑制Notch通路可明显抑制CD4+T细胞IL-22的分泌，这些结果提示异常表达的Sirt1可能通过Notch通路调节Th22细胞的功能，从而参与白塞氏病的发生发展。本项目以Sirt1为切入点，探讨Sirt1通过调控Notch通路对Th22细胞功能的影响。通过上述研究将可能阐明Sirt1在白塞氏病中的作用及可能的机制，为自身免疫性葡萄膜炎的机制研究提供新的思路，为其治疗提供新的作用靶点。