The pulmonary neuroepithelial body microenvironment represents an underestimated multimodal component in airway sensory pathways

Exciting new imaging and molecular tools, combined with state-of-the-art genetically modified mouse models, have recently boosted interest in pulmonary (vagal) sensory pathway investigations. In addition to the identification of diverse sensory neuronal subtypes, visualization of intrapulmonary projection patterns attracted renewed attention on morphologically identified sensory receptor end-organs, such as the pulmonary neuroepithelial bodies (NEBs) that have been our area of expertise for the past four decades. The current review aims at providing an overview of the cellular and neuronal components of the pulmonary NEB microenvironment (NEB ME) in mice, underpinning the role of these complexly organized structures in the mechano- and chemosensory potential of airways and lungs. Interestingly, the pulmonary NEB ME additionally harbors different types of stem cells, and emerging evidence suggests that the signal transduction pathways that are active in the NEB ME during lung development and repair also determine the origin of small cell lung carcinoma. Although documented for many years that NEBs appear to be affected in several pulmonary diseases, the current intriguing knowledge on the NEB ME seems to encourage researchers that are new to the field to explore the possibility that these versatile sensor-effector units may be involved in lung pathogenesis or pathobiology.