特发性肺纤维化发病机制不明，致死率高，至今缺乏有效疗法。因此，探明肺纤维化的病理机制是寻找有效治疗方法的首要问题。众多研究表明神经内分泌系统可影响肺纤维化。我们发现切除迷走神经可减轻博来霉素诱发的肺纤维化；在病变发展过程中，迷走神经感受器-神经上皮小体（NEB）明显增生。由此，我们假设：迷走神经-神经上皮小体系统（VNS）可以感受损伤引起的微环境变化并释放生物活性物质激活巨噬细胞向M2型极化而促进肺纤维化。我们将应用组织学、分子生物学等实验技术验证：1.切除或者阻断迷走神经系统可改善肺纤维化；2.促纤维化因子TGF-β和IL-4可增强NEB的生物活性；3.神经上皮细胞可增强成纤维细胞增殖，它释放的GRP、CGRP和5-HT可增加M2型巨噬细胞并促进肺纤维化。该项目在整体和离体两个方面，奠定VNS的神经免疫机制在肺纤维化过程中的重要性，为改善或限制肺纤维化提供理论基础乃至新的治疗靶点。

Pulmonary fibrosis (PF), especially idiopathic PF is a devastating and fatal disease with increasing prevalence rate. Despite extensive research efforts, our understanding of underlying disease mechanisms is limited and currently there is no effective treatment for IPF. Therefore, identifying the mechanisms that promote this disease is greatly needed to develop novel therapeutics. Increasing evidence indicates that the neuroimmune interaction is closely related to progression of PF. Our preliminary studies demonstrate that vagotomy attenuated bleomycin induced PF in mice and the vagal sensor-neuroepithelial body (NEB) count increased in the lung following bleomycin challenge. Thus, we hypothesize that Vagal-NEB System may detect changes of microenvironment during lung injury and produce bioactive substances to activate macrophage to M2 phenotype and then promote PF. To test this hypothesis, histological, cytological and molecular biological techniques will be applied to address three specific aims : 1. vagotomy or inhibitor of ACh receptor may promote PF; 2. fibrogenic molecules (TGF-β and IL-4) improve bioactivity of NEB; 3. neuroepithelial cells promote proliferation of fibroblasts. Its product-bioactive substances (GRP, CGRP, 5-HT) promote M2 polarization and then PF. This project will determine stimulation of the vagal-NEB system promotes PF, in vitro and in vivo. Successful completion of these studies will help establish a novel neural mechanism in the pathogenesis of PF. This could yield new approaches to improve or limit chronic fibrotic lung disease, as well as open up a new research field in pathogenesis and treatment of pulmonary diseases in terms of neuroimmune interaction.