Mammalian lungs have the ability to recognize external environments by sensing different compounds in inhaled air. Pulmonary neuroendocrine cells (PNECs) are rare, multi-functional epithelial cells currently garnering attention as intrapulmonary sensors; PNECs can detect hypoxic conditions through chemoreception. Because PNEC overactivation has been reported in patients suffering from respiratory diseases - such as asthma, chronic obstructive pulmonary disease, bronchopulmonary dysplasia and other congenital diseases - an improved understanding of the fundamental characteristics of PNECs is becoming crucial in pulmonary biology and pathology. During the past decade, murine genetics and disease models revealed the involvement of PNECs in lung ventilation dynamics, mechanosensing and the type 2 immune responses. Single-cell RNA sequencing further unveiled heterogeneous gene expression profiles in the PNEC population and revealed that a small number of PNECs undergo reprogramming during regeneration. Aberrant large clusters of PNECs have been observed in neuroendocrine tumors, including small-cell lung cancer (SCLC). Modern innovation of imaging analyses has enabled the discovery of dynamic migratory behaviors of PNECs during airway development, perhaps relating to SCLC malignancy. This Review summarizes the findings from research on PNECs, along with novel knowledge about their function. In addition, it thoroughly addresses the relevant questions concerning the molecular pathology of pulmonary diseases and related therapeutic approaches.

中文翻译：

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肺神经内分泌细胞：生理学、组织稳态和疾病。

哺乳动物的肺能够通过感知吸入空气中的不同化合物来识别外部环境。肺神经内分泌细胞 (PNEC) 是一种罕见的多功能上皮细胞，目前作为肺内传感器受到关注。PNEC 可以通过化学感受检测缺氧情况。由于在患有呼吸系统疾病（例如哮喘、慢性阻塞性肺病、支气管肺发育不良和其他先天性疾病）的患者中报告了 PNEC 过度激活，因此对 PNEC 基本特征的进一步了解在肺生物学和病理学中变得至关重要。在过去十年中，小鼠遗传学和疾病模型揭示了 PNEC 参与肺通气动力学、机械感应和 2 型免疫反应。单细胞 RNA 测序进一步揭示了 PNEC 群体中的异质基因表达谱，并揭示了少数 PNEC 在再生过程中经历了重编程。在神经内分泌肿瘤（包括小细胞肺癌 (SCLC)）中观察到异常的大簇 PNEC。影像分析的现代创新使得在气道发育过程中发现 PNEC 的动态迁移行为成为可能，这可能与 SCLC 恶性肿瘤有关。本综述总结了 PNEC 研究的结果，以及有关其功能的新知识。此外，它还彻底解决了有关肺部疾病分子病理学和相关治疗方法的相关问题。