黑色素瘤缺失蛋白1(AIM1)调控IL-6表达在克罗恩病发病中的作用机制研究

克罗恩病是一种病程多迁延、反复发作的炎症性肠病，其具体的发病机制仍然不是十分清楚。白细胞介素6（IL-6）是一种多功能的细胞因子，在克罗恩病中扮演了重要角色。黑色素瘤缺失蛋白1（AIM1）是一种非晶状体晶状体蛋白，目前除了其抑制肿瘤外的其它功能知之甚少。我们新近的研究成果发现两栖类非晶状体晶状体蛋白在激发天然免疫中发挥了重要作用；此外，我们初步的前期结果发现在巨噬细胞中敲除AIM1后会抑制IL-6的表达，同时AIM1敲除小鼠的结肠炎严重程度明显低于野生型小鼠。在此基础上，本项目拟深入研究肠组织中AIM1表达水平同克罗恩病的相关性；AIM1在TNBS诱导的克罗恩病小鼠模型中调控IL-6表达影响肠道免疫反应的功能与机制；AIM1调控IL-6表达的分子机制。研究结果有助于揭示AIM1在克罗恩病发生中的功能与机制，为深入理解克罗恩病的发病机制提供新见解。

Crohn's disease is an inflammatory bowel disease with a prolonged course and recurrent episodes. However, the specific pathogenesis of Crohn's disease is still unclear. Interleukin 6 (IL-6) is a pleiotropic cytokine that plays an important role in Crohn's disease. Absent in melanoma 1 (AIM1) is a non-lens betagamma-crystallin protein. Except for its role as a tumor suppressor, the functions of AIM1 remain unclear. We recently have found that amphibian non-lens betagamma-crystallin protein play an important role in triggering innate immunity. In addition, our preliminary results showed that the expression of IL-6 was significantly inhibited in AIM1-knockout macropahge, and the AIM1-deficent mice were more tolerant to DSS-induced colitis than wild-type mice. On this basis, this project intends to further study: (1) the correlation between intestinal AIM1 expression level and Crohn's disease; (2) the function and mechanism of AIM1 disturbing intestinal immune response in TNBS-induced Crohn's disease mouse model by regulating IL-6 expression; (3) the molecular mechanisms of AIM1 regulating IL-6 expression. Our study would provide insight into the function and mechanism of AIM1 in Crohn's disease, and provide new ideas for a deeper understanding of the pathogenesis of Crohn's disease.