Neuro-immune interactions during development of pulmonary fibrosis

Abstract

Pulmonary neuroendocrine cells are widely distributed throughout the airway mucosa of mammals. They may exist as solitary cells or aggregate to form NeuroEpithelial Bodies (NEBs), which are important in early lung development. Pulmonary Fibrosis (PF) is a devastating disease caused by various pulmonary insults. The lung repair after injury is a complex process which involves a network of interactions among mediators, cytokines, and growth factors of inflammatory, endothelial, and epithelial cell origin. These interactions lead to lung remodeling, deposition of collagen, limitation of gas exchange, and dyspnea. The vagus nerve is related to each component of this network. Increasing evidence indicates that the NEB-Vagal System (NVS) plays an important role in neuro-immune interactions. NEBs are richly innervated and connect with the central nervous system through vagal afferent and efferent nerves. Stimulation of the vagus nerve in patients significantly increases the levels of TGF-β in plasma, a substance that promotes fibrosis. Based on current information, lung injury may activate the NVS, which then leads to PF via fibrogenic cells and molecules. Therefore, over-activation of the NVS could contribute to disease progression.