Abstract
Respiratory diseases are frequently characterised by epithelial injury, airway inflammation, defective tissue repair, and airway remodelling. This may occur in a subacute or chronic context, such as asthma and chronic obstructive pulmonary disease, or occur acutely as in pathogen challenge and acute respiratory distress syndrome (ARDS). Despite the frequent challenge of lung homeostasis, not all pulmonary insults lead to disease. Traditionally thought of as a quiescent organ, emerging evidence highlights that the lung has significant capacity to respond to injury by repairing and replacing damaged cells. This occurs with the appropriate and timely resolution of inflammation and concurrent initiation of tissue repair programmes. Airway epithelial cells are key effectors in lung homeostasis and host defence; continual exposure to pathogens, toxins, and particulate matter challenge homeostasis, requiring robust defence and repair mechanisms. As such, the epithelium is critically involved in the return to homeostasis, orchestrating the resolution of inflammation and initiating tissue repair. This review examines the pivotal role of pulmonary airway epithelial cells in initiating and moderating tissue repair and restitution. We discuss emerging evidence of the interactions between airway epithelial cells and candidate stem or progenitor cells to initiate tissue repair as well as with cells of the innate and adaptive immune systems in driving successful tissue regeneration. Understanding the mechanisms of intercellular communication is rapidly increasing, and a major focus of this review includes the various mediators involved, including growth factors, extracellular vesicles, soluble lipid mediators, cytokines, and chemokines. Understanding these areas will ultimately identify potential cells, mediators, and interactions for therapeutic targeting.
Highlights
Respiratory diseases are frequently characterised by epithelial injury, airway inflammation, defective tissue repair, and airway remodelling
A quiescent organ at baseline the lungs have a significant reparative capacity in response to injury [2] (Figure 1A), but dysregulated inflammation and aberrant or defective repair mechanisms are increasingly linked to the pathobiology of several diseases including COPD, asthma pulmonary fibrosis and acute respiratory distress syndrome (ARDS) [3]
Vitamin D deficiency is associated with increased risks of pulmonary viral infection [60], with data suggesting that vitamin D may enhance type I interferon responses, endogenous mediators of antiviral immunity
Summary
Lungs are continually exposed to infections, toxins, and airborne pollutants that stress homeostasis. Respiratory disorders cause a vast burden of global disease and are among the leading causes of death worldwide [1]. A quiescent organ at baseline the lungs have a significant reparative capacity in response to injury [2] (Figure 1A), but dysregulated inflammation and aberrant or defective repair mechanisms are increasingly linked to the pathobiology of several diseases including COPD, asthma pulmonary fibrosis and acute respiratory distress syndrome (ARDS) [3]. Given that the pulmonary epithelium is central to host defence, homeostasis, and disease biology, this review highlights the role of airway epithelium in repair, with a particular focus on the mediators involved.
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