Dissecting macrophage regulation of lung epithelial regeneration

剖析巨噬细胞对肺上皮再生的调节

• 批准号: MR/X019314/1
• 负责人: Christopher Lucas
• 金额: $ 238.26万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX019314%2F1
• 关键词: Dissecting; macrophage; regulation; lung; epithelial

Lungs are continually exposed to infections and toxins, which frequently damage the internal lining of the lungs, the epithelium. Widespread epithelial damage compromises lung function and occurs in fatal lung injury, including COVID-19 lung disease. It is therefore vital that the lung can regenerate and repair itself to ensure optimum functioning and protect against infections. But the regeneration process is very poorly understood and functions abnormally in several human lung conditions. No existing treatments promote lung regeneration. Understanding the process of how the lung naturally regenerates after injury may help develop new treatments that promote lung regeneration after serious infection or damage.It is known that following lung injury, cells from the body's immune system called macrophages increase in numbers and are critical to accelerate healing. But what sort of macrophage promotes epithelial regeneration and how they achieve this is not clear. This study will investigate which macrophages promote lung epithelial regeneration (focusing on 'interstitial macrophages'), how the numbers of these macrophages are increased after lung injury, and the methods these macrophages use to coordinate regeneration of the lung. This research will be achieved by laboratory-based investigation and involve using immune cells and epithelial cells isolated from human lungs and using models of lung injury and repair. The research will be carried out primarily by Dr Christopher Lucas, a consultant in respiratory medicine and researcher based at the University of Edinburgh. This work will be performed mainly at the newly formed Institute for Regeneration and Repair, the world's largest institute dedicated to tissue regeneration. The work will be supported by scientists at the University of Edinburgh, including Dr Jenkins, Dr Bain, Dr Gray and Prof. Walmsley who are world experts in macrophages and lung inflammation. Part of the work will also be delivered by national and international collaborations with the Carlin group at the Beatson UK, and the Perry Laboratory at Sloan Kettering in New York, USA, to benefit from those team's expertise in analysing immune cell responses.By using this unique combination of scientists, resources and novel research ideas we aim to identify new mechanisms of lung regeneration to help develop new treatments that will promote lung regeneration after serious infection or damage.

肺部持续暴露于感染和毒素，这经常损害肺的内层，即上皮。广泛的上皮损伤会损害肺功能，并发生在致命的肺损伤中，包括COVID-19肺病。因此，至关重要的是，肺可以再生和自我修复，以确保最佳功能并防止感染。但是再生过程知之甚少，在几种人类肺部疾病中功能异常。没有现有的治疗促进肺再生。了解损伤后肺如何自然再生的过程可能有助于开发新的治疗方法，促进严重感染或损伤后的肺再生。众所周知，肺损伤后，来自人体免疫系统的巨噬细胞数量增加，对加速愈合至关重要。但是什么样的巨噬细胞促进上皮再生以及它们如何实现这一点尚不清楚。本研究将研究哪些巨噬细胞促进肺上皮再生（重点是“间质巨噬细胞”），这些巨噬细胞的数量如何在肺损伤后增加，以及这些巨噬细胞用于协调肺再生的方法。这项研究将通过基于实验室的研究来实现，并涉及使用从人类肺部分离的免疫细胞和上皮细胞以及使用肺损伤和修复模型。这项研究将主要由爱丁堡大学的呼吸医学顾问和研究人员克里斯托弗·卢卡斯博士进行。这项工作将主要在新成立的再生和修复研究所进行，该研究所是世界上最大的组织再生研究所。这项工作将得到爱丁堡大学科学家的支持，包括Jenkins博士，Bain博士，Gray博士和Walmsley教授，他们是巨噬细胞和肺部炎症的世界专家。部分工作还将通过与英国Beatson的Carlin小组和美国纽约Sloan Kettering的佩里实验室的国家和国际合作来完成，以受益于这些团队在分析免疫细胞反应方面的专业知识。通过使用这种独特的科学家组合，资源和新的研究思路，我们的目标是确定肺再生的新机制，以帮助开发新的治疗方法，这将促进严重的肺再生后，感染或损伤。