An Airway-Centric View of Idiopathic Pulmonary Fibrosis.
An Airway-Centric View of Idiopathic Pulmonary Fibrosis.
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特发性肺纤维化的以气道为中心的观点。
DOI：
10.1164/rccm.202109-2219pp
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发表时间：
2022
影响因子：
24.7
通讯作者：
Schwartz,DavidA
中科院分区：
文献类型：
--
作者：
Stancil,IanT;Michalski,JacobE;Schwartz,DavidA
特发性肺纤维化（IPF）是无数空间和时间上不同的微观病灶的适应不良修复的累积表现，以应对复发性肺损伤。然而，IPF 适应不良修复的关键驱动因素、必需细胞和关键机制仍然难以捉摸。数十年的研究重点是肺泡损伤和肺泡间质串扰及其与 II 型肺泡上皮缺陷、成纤维细胞活化和进行性肺纤维化（导致器官功能减弱）的关系 (1-3)。此外，已有充分证据表明免疫细胞和内皮细胞类型与 IPF 有关 (4, 5)。然而，即使有气道特异性受累的重要证据，对 IPF 气道上皮的描述也不完整 (6-9)。对 IPF 远端气道功能障碍的最早描述之一是在四十多年前 (7)；然而，自从这一发现以来，我们对远端气道上皮对 IPF 发病机制贡献的理解并没有跟上肺部其他组织类型或解剖区域的步伐。健康的远端（此处定义为气道，内径 2 毫米）气道上皮主要由祖细胞、产生粘液的细胞和多纤毛细胞群组成。在 IPF 中观察到的祖细胞多样性 (10) 的大幅增加 (10)、粘液的错误表达 (11) 以及可能的异常纤毛 (12) 重新激发了人们对远端气道上皮的兴趣。
Idiopathic pulmonary fibrosis (IPF) is the cumulative manifestation of countless spatially and temporally distinct microscopic foci of maladaptive repair in response to recurrent lung injury. However, the key drivers, essential cells, and critical mechanisms of maladaptive repair in IPF remain elusive. Decades of research has focused on alveolar injury and alveolar–mesenchymal cross-talk and their association with type II alveolar epithelial defects, fibroblast activation, and progressive lung fibrosis resulting in diminished organ function (1–3). In addition, it has been well documented that immune and endothelial cell types are involved in IPF (4, 5). However, the airway epithelium has been incompletely described in IPF, even with significant evidence of airway-specific involvement (6–9). One of the first descriptions of distal airway dysfunction in IPF was more than four decades ago (7); however, since that discovery, our understanding of distal airway epithelial contributions to IPF pathogenesis has not kept pace with other tissue types or anatomical regions of the lung. Healthy distal (defined here as an airway, 2 mm in internal diameter) airway epithelium is composed primarily of progenitor, mucus-producing, and multiciliated cell populations. Large increases in progenitor population diversity (10), misexpression of mucus (11), and possible aberrant ciliation (12) observed in IPF have reinvigorated interest in the distal airway epithelium.