Eosinophil and macrophage crosstalk defines cell survival and modulates local tissue niche.

人体由组织组成，如心脏或皮肤，由多种不同的细胞类型组成：组织细胞和免疫细胞。免疫细胞是保护身体免受细菌和病毒侵害的细胞，但它们也在保持我们的组织健康方面发挥作用。不同类型的免疫细胞在这个过程中相互沟通和指导。这种交流的中断通常会使人生病或使受伤需要更长的时间才能愈合。在这项研究中，我探索了两种类型的免疫细胞，巨噬细胞和嗜酸性粒细胞之间发送的信息，以及这种通信如何改变组织健康。巨噬细胞是体内的大型免疫细胞，可以感知组织中的问题，例如损伤和细菌。嗜酸性粒细胞是最有名的，以保护我们免受寄生虫，但他们有一些其他非常重要的功能，在体内。嗜酸性粒细胞携带大量不同的信号分子在其特殊的隔室，称为颗粒。根据来自其他细胞的信息，嗜酸性粒细胞释放回选定的信号分子以执行其功能。例如，在肝损伤期间，肝细胞向嗜酸性粒细胞发送信息，使其到达肝脏。一旦它们到达，嗜酸性粒细胞就会与肝细胞通讯以帮助它们愈合。同样，我们知道嗜酸性粒细胞与巨噬细胞交谈，这种交流对于维持健康的组织甚至健康的体重非常重要。因此，细胞之间的沟通对于保持健康的组织和身体至关重要。如果这种对话被打断，细胞就会被误导，嗜酸性粒细胞通常会在一个组织中大量聚集。这种过度拥挤促使嗜酸性粒细胞发出局部错误的信号，然后导致组织损伤，如哮喘。在大多数情况下，我们不了解导致嗜酸性粒细胞聚集在健康组织中的信息。在英国，超过1000万人患有嗜酸性粒细胞相关疾病，一些危及生命，大多数改变生命。在过去的20年里，因过敏反应，严重过敏反应而入院的人数增加了6倍。嗜酸性粒细胞介导的疾病的频率不断上升，需要快速和新的诊断和治疗方法。了解细胞通讯的基本规则是实现这些目标的第一步和基本步骤。我有一个模型，其中一个组织中的巨噬细胞有缺陷，在这个模型中，我观察到嗜酸性粒细胞数量和存活率的显著变化。这是一个非常新颖的观察。我们知道嗜酸性粒细胞直接与巨噬细胞对话，但巨噬细胞对嗜酸性粒细胞的回复或初始信息并不常见。我将使用这个模型来了解这些细胞是如何交流的，具体来说：1。巨噬细胞的缺陷如何影响局部组织和嗜酸性粒细胞的数量和存活？2.什么信息是用来交流的，它们可以用来控制体内的嗜酸性粒细胞吗？3.我可以操纵这种通信以防止组织损伤吗？我的数据显示，巨噬细胞-嗜酸性粒细胞通讯是正常组织功能的核心。我发现了一个可能导致组织中嗜酸性粒细胞增多的信号。这是非常令人兴奋的，因为这些细胞之间的这种信息是无法识别的。目的是了解这种通信如何维持正常的组织功能，以及它如何导致疾病和组织损伤。

Human bodies are made up from tissues, such as heart or skin, which consist of multiple different cells types: the cells of the tissue and immune cells. Immune cells are the cells that protect the body from, for example, bacteria and viruses, but they also play a role in keeping our tissues healthy. Different types of immune cells communicate and instruct each other in this process. Interruption in this communication often makes people ill or make an injury take longer to heal. In this research, I explore the messages sent between two types of immune cells, macrophages and eosinophils and how that communication changes tissue health.Macrophages are large immune cells in your body that sense problems in your tissue, such as damage and germs. Eosinophils are best known to protect us from parasites, but they have number of other very important functions in the body. Eosinophils carry large amount of different signalling molecules in their special compartments, called granules. Depending on the messages from other cells, eosinophils release back selected signalling molecule to perform their functions. For example, during liver damage, liver cells send message to eosinophils to come to the liver. Once they arrive, eosinophils communicate with the liver cells to help them heal. Similarly, we know that eosinophils talk to macrophages and this communication is important for maintaining healthy tissues and even a healthy body weight. So, communication between cells is essential to keep healthy tissues and body. If this conversation is interrupted, cells are misdirected and often eosinophils gather together in high numbers in one tissue. This overcrowd pushes eosinophils to send locally wrong signals, which then cause tissue damage, like during asthma. In most cases, we do not understand the messages causing eosinophil gathering in healthy tissues. Over 10 million people in UK suffer from eosinophil related diseases, some life-threatening and most life-altering. Hospital admissions for anaphylaxis, severe allergic reactions, increased by 6-fold in the last 20 years. The rising frequency of eosinophil-mediated diseases requires quick and new diagnostic and treatment methods. Understanding basic rules of cells communication is the first and fundamental step towards these goals. I have a model in which macrophages in one tissue are defective and, in this model, I have observed notable changes in eosinophils numbers and survival. This is a very novel observation. We know that eosinophil talk directly to macrophages, but macrophages replies or initial messages to eosinophils are not often seen. I will use this model to understand how these cells communicate, specifically:1. How do defects in macrophages affects local tissue and eosinophil numbers and survival?2. What messages are used to communicate, and can they I use of them to control eosinophils in the body? 3. Can I manipulate this communication to prevent tissue damage?My data shows macrophage-eosinophil communication to be at the heart of normal tissue function. I have identified a candidate signal that might be responsible for high numbers of eosinophil in the tissue. This is very exciting because such messages between these cells are not recognised. The aim is to understand how this communication maintains normal tissue functioning and how it can lead to disease and tissue damage.