Lung inflammation and tissue scarring are driven by immune cells, but a new suspect has emerged: the nerves and their supporting glial cells that weave through airway tissue. These glial cells are known to regulate immune responses in the skin and gut, but their role in the lung has been largely overlooked. This project aims to fill that gap by mapping how lung glia interact with immune cells during health and in inflammatory disease. The researchers will use single-cell RNA sequencing, advanced imaging, and viral tools to selectively manipulate glia in mouse models, then confirm key findings in human lung tissue. This is fundamental science. There is no immediate clinical application. But understanding how glia shape lung immunity could eventually point to new drug targets for chronic conditions such as asthma, fibrosis, or post-infection inflammation. Similar discoveries about glial-immune crosstalk in other tissues have already opened unexpected therapeutic avenues. If glia prove to be central regulators of lung inflammation, they may offer a way to treat respiratory disease without directly targeting immune cells.
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Maintenance of barrier tissue homeostasis and function depends on the integrated activity of epithelial, immune and neuroglial cellular systems with the local microbiota. In the lung, disruption of this balance, either spontaneous or in response to infection or inhaled antigens, has severe consequences for human health, manifested as respiratory inflammation and detrimental tissue remodelling of poorly understood aetiology. Recent reports in other barrier tissues uncovered roles for peripheral glia in homeostasis, immunity, and wound repair suggesting that these cells represent important regulatory nodes for maintaining and restoring the function of all barrier sites; pointing to a potential role of intrinsic neuroglial networks in shaping lung immunity, both at steady state and during disease. This proposal will employ state-of-the-art single cell RNA sequencing, imaging techniques and viral vector-mediated lung glia-specific in vivo targeting in conjunction with mouse models of lung inflammation and human tissue samples to understand how lung glia regulate immune homeostasis and inflammation and to determine underlying pathways that control their interaction with other lung tissues in health and disease. This research will provide fundamental knowledge that will likely advance the development of therapies for lung inflammatory conditions and inform our understanding of neuroglial-immune interactions in other barrier tissues.
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