Th1（CD4+IFN-γ+T）细胞浸润胰岛导致1型糖尿病胰岛炎。NLRP3炎症小体（NLRP3/Caspase-1/IL-1β）控制CD4+T细胞向Th1细胞分化。DPP-4抑制剂在体内主要通过升高GLP-1水平起作用。我们研究发现DPP-4抑制剂保护1型糖尿病患者胰岛功能，下调Th1细胞。我们预试验结果显示GLP-1类似物（利拉鲁肽）通过JAK2/STAT4信号，减少IFN-γ分泌，下调Th1免疫。我们推测：GLP-1类似物通过NLRP3炎症小体阻断CD4+T细胞向Th1细胞分化，减轻1型糖尿病胰岛炎。本研究将明确GLP-1类似物（利拉鲁肽）对胰岛炎的影响、如何下调NLRP3/Caspase-1/IL-1β信号及阻断CD4+T细胞向Th1细胞分化，探索GLP-1类似物减轻1型糖尿病胰岛炎的具体机制，为1型糖尿病的免疫治疗提供新思路。

Th1 (CD4+IFN-γ+T) cells infiltrate islet and cause insulitis in type 1 diabetes. NLRP3 inflammasome (NLRP3/Caspase-1/IL-1β) is the main signal to control CD4+T cell to differentiate into Th1 cells. DPP-4 inhibitor plays its role mainly by increasing GLP-1 levels in vivo. In our previous study, we found that DPP-4 inhibitor treatment protects islet function of patients with type 1 diabetes and down-regulates Th1 immune response via reducing IFN-γ secretion in CD4+T cells. In preliminary experiment, we found that GLP-1 analogue (liraglutide) has the effect to reduce IFN-γ secretion by down-regulating the JAK2/STAT4 signaling in T cells in vitro. We hypothesize that GLP-1 analogue alleviates insulitis in type 1 diabetes by blocking NLRP3 inflammasome, which controls CD4+T cell to differentiate into Th1 cells. In this project, we will study the effect of liraglitpin on insulitis and the mechanism to downregulate NLRP3/Caspase-1/IL-1β signaling pathway and block CD4+T cell to differentiate into Th1 cells in type 1 diabetes. We will explore the mechanism of GLP-1 analogue to alleviate insulitis, which will provide new sight for the immunotherapy of type 1 diabetes.