Member of the German Center for Lung Research (DZL), Institute of Lung Health and Immunity and Comprehensive Pneumology Center with the CPC-M BioArchive, Helmholtz Zentrum München GmbH, 81377 Munich, Germany.
Cells. 2022 Mar 19;11(6):1050. doi: 10.3390/cells11061050.
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with incompletely understood aetiology and limited treatment options. Traditionally, IPF was believed to be mainly caused by repetitive injuries to the alveolar epithelium. Several recent lines of evidence, however, suggest that IPF equally involves an aberrant airway epithelial response, which contributes significantly to disease development and progression. In this review, based on recent clinical, high-resolution imaging, genetic, and single-cell RNA sequencing data, we summarize alterations in airway structure, function, and cell type composition in IPF. We furthermore give a comprehensive overview on the genetic and mechanistic evidence pointing towards an essential role of airway epithelial cells in IPF pathogenesis and describe potentially implicated aberrant epithelial signalling pathways and regulation mechanisms in this context. The collected evidence argues for the investigation of possible therapeutic avenues targeting these processes, which thus represent important future directions of research.
特发性肺纤维化（IPF）是一种病因尚不完全清楚且治疗选择有限的致命疾病。传统上，IPF 主要被认为是由肺泡上皮的反复损伤引起的。然而，最近的几条证据线表明，IPF 同样涉及到异常的气道上皮反应，这对疾病的发展和进展有重要贡献。在这篇综述中，我们根据最近的临床、高分辨率成像、遗传和单细胞 RNA 测序数据，总结了 IPF 中气道结构、功能和细胞类型组成的改变。我们还全面概述了指向气道上皮细胞在 IPF 发病机制中起重要作用的遗传和机制证据，并描述了在此背景下可能涉及的异常上皮信号通路和调节机制。收集到的证据支持针对这些过程的可能治疗途径的研究，这是未来研究的重要方向。
