Barrier glia as regulators of lung immunity

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.