Spatiotemporal Cellular Networks Maintain Immune Homeostasis in the Lung

A dynamic and intricately connected tissue-resident immune cell network continuously monitors the lungs, which are incessantly subjected to external environmental insults. The lungs are protected by the respiratory epithelium, which not only serves as a physical barrier through mucociliary mechanisms, but also a reactive one that can release cytokines, chemokines, and other defence proteins in response to danger signals. In the maintenance of pulmonary homeostasis in health, the lung-resident immune cell network instructs tolerance to innocuous particulates and can rapidly and efficiently drive immunity and memory to pathogenic antigens. This review examines the spatiotemporal dynamics that underlie the exquisite network of highly specialised immune cells and their mediators in the support of pulmonary tissue homeostasis and effective lung immunity in health. In particular, this review examines the specialised immune cells that reside in distinct populations within the diverse compartments of the lung, and the molecular signals that retain and recruit lung resident immune cells, to further our understanding of how these can be targeted therapeutically to return inflamed or diseased lungs to homeostasis.