Regulation of Intestinal Dendritic Cell Development and Function

我们肠道中的免疫系统面临着巨大的挑战，因为它必须在不损害肠道健康的情况下识别、攻击和摧毁潜在的有害传染病。然而，它还必须确保它不会对食物或生活在我们肠道中的无害细菌发动类似的攻击，这些细菌对我们的健康至关重要。然而，这些无害的材料并不只是被忽视，因为故意和积极的过程被触发，以确保整个免疫系统不会做出反应。这就是所谓的“耐受性”，大多数人在免疫攻击和耐受性之间保持着健康的平衡。对无害食物或肠道细菌的不适当攻击可能会导致慢性炎症，如乳糜泻或克罗恩病，而无效的免疫反应意味着肠道感染仍然是全球发病率和死亡率的主要原因。通过了解肠道免疫系统如何决定如何反应，我们希望找到新的方法来增强对肠道感染的疫苗接种时的反应，并开发治疗炎症性肠道疾病的新药。被称为树突状细胞的细胞在免疫反应的各个方面都是至关重要的，因为它们决定了是否发生主动免疫或耐受。他们通过解释来自环境的信号并指示T淋巴细胞如何对进入人体的不同异物做出反应来做到这一点。由于有几种不同类型的树突状细胞，每种都有不同的作用，人们认为这可以被用来故意操纵疾病中的免疫反应或用于疫苗。肠道中含有许多树突状细胞，它们在控制免疫反应中起着重要作用。然而，对它们的研究一直很困难，部分原因是它们与身体其他部位发现的细胞非常不同，也因为它们被与其他类型的细胞混淆。我们最近开发了更精确的方法来研究树突状细胞，这种细胞存在于肠道的衬里，也就是肠道中异物最多进入的部分，需要首先决定如何反应。这使我们能够识别新的树突状细胞，这些细胞以前没有被研究过，它们对不同类型的免疫反应的贡献也不清楚。在这个项目中，我们将在这一初步工作的基础上，更多地了解在肠道中发现的树突状细胞，使用一系列复杂的技术来研究不同的群体是如何相互关联的，并研究当需要耐受或主动免疫时，它们各自的行为方式。我们在该领域拥有长期的经验，并将与瑞典、法国、比利时和美国的国际领导人合作，使我们能够获得无与伦比的方法组合。因此，我们希望对一群特征不佳的细胞获得独特的见解，这些细胞对了解肠道及其免疫系统至关重要。

The immune system in our intestine faces a formidable challenge, as it has to recognise, attack and destroy potentially harmful infectious agents, without compromising the health of the gut. However, it also has to ensure that it does not mount similar attacks against food or the innocuous bacteria that live in our intestine and which are essential for our health. However these harmless materials are not just ignored, as deliberate and active processes are triggered to make sure that the entire immune system cannot respond. This is called 'tolerance' and most people maintain a healthy balance between immune attack and tolerance. Inappropriate attacks on harmless foods or bacteria in the gut can cause chronic inflammation, such as coeliac disease or Crohn's disease, while ineffective immune responses mean intestinal infections remain major causes of morbidity and mortality worldwide. By understanding how the intestinal immune system decides how to react, we hope to find new ways of boosting responses when vaccinating against intestinal infections, and to develop new medicines for treating inflammatory bowel diseases. Cells called dendritic cells are crucial in all aspects of the immune response, as they decide whether active immunity or tolerance occurs. They do this by interpreting signals from the environment and instructing T lymphocytes how to react to the different foreign materials which enter the body. As there are several different kinds of dendritic cells, each with separate roles, it is thought that this could be exploited for deliberately manipulating immune responses in disease or for vaccines. The intestine contains many dendritic cells, where they are known to be important for controlling immune responses. However they have been difficult to study, partly because they are quite different from those found in other parts of the body and also because they have been confused with other cell types. We have recently developed more precise methods for studying the dendritic cells which are found in the lining of the intestine, the part of the gut where most foreign materials enter and where the first decisions need to be made about how to react. This has allowed us to identify new kinds of dendritic cell which have not been studied before and whose contribution to different types of immune response is not known. In this project, we will build on this initial work to understand more about the dendritic cells found in the intestine, using a mixture of sophisticated techniques to investigate how the various groups are related to each other and to study how they each behave when tolerance or active immunity is required. We have long experience in the field and will collaborate with international leaders in Sweden, France, Belgium and the USA, giving us access to an unrivalled mixture of methods. As a result, we hope to gain unique insights into a poorly characterised population of cells of critical importance for understanding the intestine and its immune system.