临床研究发现肠道炎症及渗漏性在胰岛损伤、诱发T1DM 起始过程有重要作用，而中性粒细胞胞外诱捕网(NETs)是诱发肠道炎症的重要因素，同时NETs也是T1DM自身抗原的主要来源之一。我们在前期的研究中发现，乳酸菌递呈的葡萄球菌核酸酶（SNase）能降低NOD小鼠的糖尿病发病率，我们认为一方面是乳酸菌作为益生菌对T1DM早期的调控作用，另一方面是SNase介导NETs降解对肠道内炎症起了负向调节作用，最终逆转了T1DM进程。基于此研究结果，本申请拟对SNase介导NETs降解在T1DM防治中的作用及其免疫机制做进一步的深入研究，为NETs作为一个新的靶标防治自身免疫性疾病提供研究基础。

Clinical trials have found that the inflammation and permeability of gut are associated with pancreatic beta-cell autoimmunity and type 1 diabetes mellitus (T1DM). The release of neutrophil extracellular traps (NETs) contributes to the intestinal damage and is also an important source of autoantigens in patients with T1DM. Our previous study found that oral administration of L.lactis-expressing Staphylococcal nuclease（SNase）can reduce the incidence of T1DM in NOD mice.We thought that both L.lactis and SNase-mediated NETs degradation play a negative regulatory role in T1DM earlier development. Based on the results, we intend to study the immune mechanism of SNase-mediated NETs degradation resistance to T1DM and provide experimental foundation for NETs, a new target, in prevention of autoimmune diseases.