IL-35及其诱导的调节性T细胞在SjSEA治疗2型糖尿病中的作用机制研究

2型糖尿病是由于胰岛素抵抗导致血糖水平持续升高的慢性炎症性疾病。日本血吸虫可溶性虫卵抗原（SjSEA）可用于治疗2型糖尿病并与其诱导的调节性T细胞相关。然而，调节性T细胞的作用机制尚不明确。文献报道，IL-35由调节性T细胞分泌后维持其抑制功能并将传统T细胞转化为iTr35。申请人前期研究发现SjSEA诱导机体高表达IL-35，而IL-35下调与2型糖尿病有关，能使IL-35上调的药物可望成为治疗2型糖尿病的靶点。提示IL-35可能参与SjSEA治疗2型糖尿病。基于此，本项目拟验证SjSEA对IL-35和iTr35的作用；解析体外IL-35和iTr35参与SjSEA对脂肪细胞的作用；探究体内IL-35参与SjSEA治疗2型糖尿病的作用。结合SjSEA有利于创伤愈合检测巨噬细胞极化等机制，从而阐明IL-35参与SjSEA治疗2型糖尿病的作用及机制，为2型糖尿病的治疗提供新的思路和分子靶点。

Type 2 diabetes is a chronic inflammatory disease caused by insulin resistance that causes a continuous rise in blood sugar levels. It has been reported that Schistosoma japonicum soluble egg antigen (SjSEA) protects against type 2 diabetes in Leprdb/db mice by enhancing regulatory T cells. However, the mechanism of regulatory T cells is not clear. IL-35 has been described to be produced predominantly by regulatory T cells and led to the conversion of conventional T cells into IL-35-induced regulatory T cells (iTr35). Our previous results demonstrated that SjSEA can induce high expression of IL-35 in the human and mice. And down regulation of IL-35 is related to type 2 diabetes, then the drugs that up regulate IL-35 are expected to be the targets for the treatment of type 2 diabetes. Based on the above, we proposed that IL-35 may be involved in the treatment of type 2 diabetes by SjSEA. The project is to be elaborated from the following three aspects: Verify the effect of SjSEA on IL-35 and iTr35; Analysis of the role of IL-35 and iTr35 induced by SjSEA on adipocytes in vitro; To explore if SjSEA protect against type 2diabetes through increasing IL-35 and mediating iTr35 conversion in vivo. Furthermore, SjSEA is beneficial to wound healing, which may be related to macrophage polarization. To further elucidate the mechanism of SjSEA enhancing the sensitivity of adipocytes to insulin sensitivity, it provides new ideas and molecular targets for the treatment of Type 2 diabetes.