溃疡性结肠炎是一种慢性炎症性疾病，其发病机制与肠黏膜的异常免疫应答相关。患者在直肠及结肠近端具有反复发作的黏膜炎症。在肠道免疫系统中，天然免疫细胞ILCs通过分泌特异细胞因子参与宿主对抗肠道病原体的过程。统计数据显示，溃疡性结肠炎病人血清及肠道黏膜组织mRNA中细胞因子IL-17a均明显高于对照组。肠道中IL-17a来源主要为CD4+的Th17细胞及ILC3细胞。我们前期研究发现，磷酸酶Wip1正向调控Th9细胞的发育分化，而不影响Th17细胞，但磷酸酶Wip1缺失小鼠的溃疡性结肠炎明显加重且肠道组织中IL-17a水平明显增加。因此，我们推测磷酸酶Wip1通过影响天然免疫ILC3细胞分泌IL-17a调控溃疡结肠炎。并将通过动物模型、细胞及分子实验阐明Wip1负向调控ILC3细胞分泌IL-17a的分子机制。这将为我们在临床上寻找反映并预测溃疡性结肠炎病程的分子及药物靶点提供非常有价值的信息。

Ulcerative colitis is a chronic inflammatory disease that affects the colon and its pathogenesis is believed to involve aberrant immune response of the intestinal mucosa. Patients have repeated mucosal inflammation in the rectum and proximal segments of the colon. In intestinal immunity system, innate lymphoid cells (ILCs) have been described in host resistance to intestinal pathogens by secreting specific cytokines. Statistical data have shown that serum IL-17a and mucosal RNA expression of IL-17a are both higher than healthy controls. Therefore, we hypothesized that phosphatase Wip1 regulates ulcerative colitis by affecting the secretion of IL-17a in ILC3 cells. And we’ll use animal models, cell experiments and molecular experiments to elucidate how Wip1 negatively regulates IL-17a secretion in ILC3 cells. This study will provide us with valuable information for reflecting and predicting the clinical course of ulcerative colitis and finding a therapeutic target.