The crosstalks between immune cells, bacteria and epithelial cells in the intestine: elucidating their cellular and molecular mechanisms

人体肠道是一个复杂的器官，它的正常功能对整个身体的健康和疾病有着重要的影响。肠道主要有三个部分：(1)免疫系统，其主要功能是防止感染；(2)上皮层，它与皮肤类似，在我们的细胞和外界环境之间形成屏障；(3)以及微生物群，它是生活在我们肠道中的多种细菌、病毒、真菌和寄生虫的集合（例如，我们肠道中的细菌大约与人体中的细胞一样多）。这些因素之间不适当的相互作用可能影响各种疾病的发展，如炎症性肠病（IBD）、糖尿病、肥胖和癌症，这构成了一个重大的公共卫生和经济问题。IBD是这些疾病中较不突出的一种，在英国影响了62万人（Natalie et al., Gastroenterology 2012）， NHS每年花费约7.2亿英镑。因此，了解免疫细胞、上皮细胞和肠道微生物群如何相互作用，以促进健康、改善和潜在地治疗疾病是至关重要的。通过这项研究计划，我们的目标是表征这3种肠道成分如何相互作用。我们感兴趣的是研究一种称为先天淋巴样细胞（ILCs）的白细胞，它在肠道中具有重要功能。这些细胞可以防止感染，但也可以促进炎症。我们想要发现哪些分子在肠上皮、先天淋巴样细胞和肠道细菌之间的通讯中是重要的。这些新分子可以作为预防/治疗/治愈肠道炎症的靶点。为了识别这些关键分子，我们开发了一种新的“体外”系统，将白细胞与肠道上皮细胞（来自小鼠和人类）以及特定细菌一起培养。这些微型肠道的三维培养皿将使我们能够研究这三种成分在肠道中发生的相互作用。这个研究项目将在伦敦国王学院开发，这是一所英国顶尖的大学，我们拥有所有的研究工具和支持，能够成功完成它。由于肠道中免疫细胞、上皮细胞和细菌之间的适当相互作用对健康至关重要，这些研究的结果可能会改善患者的生活质量，因为它们对预防和/或治疗肠道相关疾病（如IBD、糖尿病、肥胖和癌症）有潜在的影响。

The human gut is a complex organ whose proper function has major implications for health and disease of the entire body. There are three main compartments in the gut: (1) the immune system, whose main function is to protect from infections; (2) the epithelial layer, which similarly to the skin forms a barrier between our cells and the outside environment; (3) and the microbiota, which is the collection of multiple bacteria, viruses, fungi and parasites that live in our gut (for example, there are approximately as many bacteria in our gut as cells in the human body). Inappropriate interactions between these elements can influence the development of various diseases such as inflammatory bowel disease (IBD), diabetes, obesity and cancer, which constitute a significant public health and economic problem. IBD alone, which is the less prominent of these diseases, affects 620,000 people in the UK (Natalie et al., Gastroenterology 2012) and costs the NHS approximately £720 million a year. Thus, it is essential to understand how the immune cells, the epithelial cells and the gut microbiota interact in order to promote health and ameliorate and potentially treat disease. With this research programme, we aim to characterize how these 3 gut components interact. We are interested in studying a type of white blood cells called innate lymphoid cells (ILCs), which have important functions in the gut. These cells can be protective against infections, but can also promote inflammation. We want to discover which molecules are important in the communication between the intestinal epithelium, the innate lymphoid cells and the gut bacteria. These new molecules could them be used as targets to prevent/treat/cure intestinal inflammation.To identify these key molecules we developed a novel 'in vitro' system to culture white blood cells together with intestinal epithelial cells (from both mouse and human origins) and with specific bacteria. These 3D cultures of mini-guts in a dish will allow us to study the interactions between these three components as they occur in the gut.This research programme is going to be developed at King's College London, a UK leading university where we have all the research tools and support to be able to successfully complete it.As proper interactions between immune cells, epithelial cells and bacteria in the gut are critical for health, the results from these studies could lead to the improvement of patient's quality of life due to their potential impact on prevention and/or treatment of intestinal-associated diseases, such as IBD, diabetes, obesity and cancer.