Despite the central importance of the respiratory system, the exact mechanisms governing lung repair after severe injury remain unclear. The notion that alveolar type 2 cells (AT2s) self-renew and differentiate into alveolar type 1 cells (AT1s) does not fully encompass scenarios where these progenitors are severely affected by disease, e.g., H1N1 influenza or SARS-CoV-2 (COVID-19). Intrapulmonary p63⁺ progenitor cells, a rare cell type in mice but potentially encompassing more numerous classic basal cells in humans, are activated in such severe injury settings, proliferating and migrating into the injured alveolar parenchyma, providing a short-term “emergency” benefit. While the fate of these cells is controversial, most studies indicate that they represent a maladaptive repair pathway with a fate restriction toward airway cell types, rarely differentiating into AT2 or AT1 cells. Here, we discuss the role of intrapulmonary basal-like p63⁺ cells in alveolar regeneration and suggest a unified model to guide future studies.

尽管呼吸系统非常重要，但严重损伤后支配肺修复的确切机制仍不清楚。肺泡2型细胞（AT2s）自我更新并分化为1型肺泡细胞（AT1s）的概念并未完全涵盖这些祖细胞受到疾病（例如H1N1流感或SARS-CoV-2（COVID- 19）。肺内p63 ⁺祖细胞是小鼠中一种罕见的细胞类型，但可能包含人类更多的经典基础细胞，在这种严重的损伤情况下会被激活，从而增殖并迁移到受伤的肺泡实质中，提供了短期的“紧急”益处。尽管这些细胞的命运是有争议的，但大多数研究表明，它们代表了适应不良的修复途径，对气道细胞类型具有命运的限制，很少分化为AT2或AT1细胞。在这里，我们讨论肺内基底样p63 ⁺细胞在肺泡再生中的作用，并提出一个统一的模型来指导未来的研究。