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Abstract: Increasing evidence of a critical role played by the bronchial epithelium in airway homeostasis is opening new therapeutic avenues. Its unique situation at the interface with the environment suggests that the subtle regulation orchestrated by the epithelium between tolerance and specific immune response might be impaired in asthma. Airway mucus is acting as a physical and a biological fluid between the environment and the epithelium, synergistically moved by the cilia. In asthma, excessive mucus production is a hallmark of airway remodeling. Since many years we tried to therapeutically target mucus hypersecretion, but actually this option is still not achieved. The present review discusses the dynamic processes regulating airway mucus production. Airway inflammation is central in current asthma management. Understanding of how the airway epithelium influences the TH2 paradigm in response to deleterious agents is improving. The multiple receptors expressed by the airway epithelium are the transducers of the biological signals induced by various invasive agents to develop the most adapted response. Airway remodeling is observed in severe chronic airway diseases and may result from ongoing disturbance of signal transduction and epithelial renewal. Chronic airway diseases such as asthma will require assessment of these epithelial abnormalities to identify phenotypic characteristics associated with predicting a clinical benefit for epithelial-directed therapies. [Copyright &y& Elsevier]

Lungs have a complex structure composed of different cell types that form approximately 17 million airway branches of gas-delivering bronchioles connected to 500 million gas-exchanging alveoli. Airways and alveoli are lined by epithelial cells that display a low rate of turnover at steady-state, but can regenerate the epithelium in response to injuries. Here, we review the key points of lung development, homeostasis and epithelial cell plasticity in response to injury and disease, because this knowledge is required to develop new lung disease treatments. Of note, canonical signaling pathways that are essential for proper lung development during embryogenesis are also involved in the pathophysiology of most chronic airway diseases. Moreover, the perfect control of these interconnected pathways is needed for the successful differentiation of induced pluripotent stem cells (iPSC) into lung cells. Indeed, differentiation of iPSC into airway epithelium and alveoli is based on the use of biomimetics of normal embryonic and fetal lung development. In vitro iPSC-based models of lung diseases can help us to better understand the impaired lung repair capacity and to identify new therapeutic targets and new approaches, such as lung cell therapy. [ABSTRACT FROM AUTHOR]