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

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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.