Dissecting macrophage regulation of lung epithelial regeneration

肺部不断地暴露在感染和毒素中，这经常破坏肺部的内层，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，包括新冠肺炎肺病。因此，至关重要的是，肺能够自我再生和修复，以确保最佳功能和预防感染。但人们对再生过程知之甚少，而且在几种人类肺部疾病中功能异常。现有的治疗方法都不能促进肺再生。了解肺损伤后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，人体免疫系统中称为巨噬细胞的细胞数量增加，对加速愈合至关重要。但目前还不清楚是哪种巨噬细胞促进了上皮细胞再生，以及它们是如何实现这一点的。本研究将探讨哪些巨噬细胞促进肺上皮细胞再生(主要是间质巨噬细胞)，这些巨噬细胞在肺损伤后数量是如何增加的，以及这些巨噬细胞用来协调肺再生的方法。这项研究将通过实验室调查来实现，涉及到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的模型。这项研究将主要由爱丁堡大学呼吸医学顾问兼研究员克里斯托弗·卢卡斯博士进行。这项工作将主要在新成立的再生与修复研究所进行，这是世界上致力于组织再生的最大研究所。这项工作将得到爱丁堡大学科学家的支持，包括詹金斯博士、贝恩博士、格雷博士和沃尔姆斯利教授，他们是巨噬细胞和肺部炎症方面的世界专家。部分工作还将通过与英国Beatson的Carlin小组和美国纽约斯隆·凯特琳的Perry实验室的国内和国际合作来实现，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、资源和新颖的研究想法的组合，我们旨在确定新的肺再生机制，以帮助开发新的治疗方法，这些新疗法将促进严重感染或损伤后的肺再生。

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.