The appendix in intestinal immunity and inflammatory bowel disease

炎症性肠病(IBD)由两种疾病组成：溃疡性结肠炎和克罗恩病。IBD在相对年轻的患者群体中会导致复发和缓解肠道炎症。我们对IBD的病因了解很少，但这些疾病涉及肠道免疫系统、遗传易感性和肠道细菌之间的相互作用。一些研究小组做出了一个无法解释的观察，那就是切除阑尾，尤其是在年轻的时候进行，可以防止溃疡性结肠炎和可能的克罗恩-S病的后期发展。如果IBD在早期阑尾切除术后确实发展，它往往不那么严重。在这个项目中，我们计划在人类和小鼠身上检查阑尾的免疫功能。阑尾是肠道免疫细胞的主要来源，但对这些细胞的性质和功能知之甚少。该项目的目的是探索从人和小鼠的阑尾分离出的免疫细胞的性质，即T淋巴细胞。将检查随年龄的变化，以解释阑尾切除术-IBD联系的年龄相关性质。这些细胞的抗炎和促炎特性将被研究，这些细胞从阑尾迁移到肠道其他部分的途径将被阐明，这些T细胞在IBD小鼠模型中的治疗潜力将被阐明。此外，这将是第一次开发和分析阑尾炎小鼠模型的研究，而阑尾炎的小鼠模型知之甚少。这些研究将使重要的观察不仅与IBD相关，而且与肠道的免疫功能相关，这将对我们从根本上理解我们如何保护自己免受恶劣环境的影响。

Inflammatory bowel diseases (IBD) consist of two entities: ulcerative colitis and Crohn's disease. IBD causes relapsing and remitting gut inflammation in relatively young populations of patients. Our understanding of causes of IBD is poor, but the diseases involve an interaction between the intestinal immune system, genetic predisposition and bacteria in the gut. One unexplained observation, made by a number of groups, is that removal of the appendix, especially if performed when young, protects against the later development of ulcerative colitis and probably Crohn s disease. If IBD does develop following earlier appendicectomy, it tends to be less severe. In this project, we plan to examine the immune features of the appendix, in human and mouse. The appendix is a major source of immune cells in the intestine but the nature of these cells and their functions are poorly understood. The aims of the project will explore the nature of immune cells, known as T lymphocytes, isolated from human and mouse appendices. Changes with age will be examined, to explain the age-related nature of the appendicectomy-IBD link. Anti- and pro-inflammatory characteristics of the cells will be studied, the migration pathways of these cells from appendix to other parts of the intestine will be clarified, and the therapeutic potential of these T cells in a mouse model of IBD will be elucidated. In addition, this will be the first study to develop and analyse a mouse model of appendicitis, which is very poorly understood. These studies will make important observations relevant not only to IBD, but to the immune function of the intestine, with implications for our fundamental understanding of the way we are protected from our hostile environment.