Regulation of Intestinal Dendritic Cell Development and Function

肠树突状细胞发育和功能的调节

• 批准号: MR/L008289/1
• 负责人: Allan Mowat
• 金额: $ 60.07万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL008289%2F1
• 关键词: Regulation; Intestinal; Dendritic; Cell; Development

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.

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感染因子。然而，它也必须确保它不会对食物或肠道中对我们健康至关重要的无害细菌发动类似的攻击。然而，这些无害的物质并没有被忽略，而是触发了蓄意和主动的过程，以确保整个免疫系统无法做出反应。这被称为“耐受性”，大多数人在免疫攻击和耐受性之间保持健康的平衡。对肠道内无害食物或细菌的不当攻击会导致慢性炎症，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世界范围内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接种肠道感染疫苗时的反应，并开发治疗炎症性肠病的新药。树突状细胞在免疫反应的各个方面都至关重要，因为它们决定是否产生主动免疫或耐受。它们通过解读来自环境的信号并指示T淋巴细胞如何对进入体内的不同外来物质做出反应来做到这一点。由于有几种不同种类的树突状细胞，每一种都有不同的作用，因此人们认为这可能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，研究它们一直很困难，部分原因是它们与身体其他部位发现的细胞大不相同，也因为它们与其他类型的细胞相混淆。我们最近开发了更精确的方法来研究在肠道内壁发现的树突状细胞，这是大多数外来物质进入肠道的部分，也是需要首先决定如何反应的地方。这使我们能够识别以前没有研究过的新型树突状细胞，它们对不同类型的免疫反应的贡献是未知的。在这个项目中，我们将在这个初步工作的基础上，更多地了解肠道中发现的树突状细胞，使用复杂技术的混合物来研究不同群体之间的关系，并研究它们在需要耐受或主动免疫时的行为。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者合作，使我们能够获得无与伦比的混合方法。因此，我们希望对一种对理解肠道及其免疫系统至关重要的特征不明确的细胞群获得独特的见解。