慢性阻塞性肺疾病（COPD）的特征是肺部持续的炎症状态和缺陷的组织修复。虽然COPD患者的炎症反应已被广泛研究并且在急性恶化期间已知会被夸大，但它对肺损伤和异常修复的贡献仍不清楚。在这项研究中，我们旨在调查炎症微环境如何影响远端肺组织修复中涉及的上皮祖细胞和它们的支持间充质细胞。我们关注了IL-1β，这是一种在COPD恶化期间升高的关键炎症介质，并使用肺上皮细胞和成纤维细胞的有机体模型评估IL-1β处理对这些细胞转录组和分泌因子的影响。虽然直接用IL-1β处理肺有机体可以促进有机体的生长，但这在成纤维细胞预处理后加入有机体治疗时会转为抑制。然后我们调查了成纤维细胞驱动的IL-1β机制，并发现了与CXCL趋化因子相关的炎症反应。我们确认这些趋化因子导致了有机体生长的受损，并发现针对它们的CXCR1/2受体或IL-1β细胞内信号转导可以减少炎症反应并恢复有机体生长。这些数据表明IL-1β通过促进不同的炎症反应改变了成纤维细胞的状态，在有机体的测试中将它们支持上皮祖细胞的功能转变为抑制的功能。这些结果意味着慢性炎症可能导致（结果是）修复受到限制，从而促进了像COPD这样的慢性炎症性疾病的发生。

Chronic Obstructive Pulmonary Disease (COPD) is characterized by a persistent inflammatory state in the lungs and defective tissue repair. While the inflammatory response in COPD patients is well characterized and known to be exaggerated during exacerbations, its contribution to lung injury and abnormal repair is still unclear. In this study, we aimed to investigate how the inflammatory microenvironment affects the epithelial progenitors and their supporting mesenchymal niche cells involved in tissue repair of the distal lung. We focused on IL-1β, a key inflammatory mediator that is elevated during exacerbations of COPD, and used an organoid model of lung epithelial cells and fibroblasts to assess the effect of IL-1β treatment on these cells' transcriptome and secreted factors. While direct treatment of the lung organoids with IL-1β promoted organoids growth, this switched towards inhibition when added as fibroblasts' pre-treatment followed by organoids treatment. We then investigated the IL-1β-driven mechanisms in the fibroblasts and found an inflammatory response related to CXCL chemokines; we confirmed that these chemokines were responsible for the impaired organoids growth and found that targeting their CXCR1/2 receptors or the IL-1β intracellular signaling reduced the pro-inflammatory response and restored organoids growth. These data demonstrate that IL-1β alters the fibroblasts' state by promoting a distinct inflammatory response, switching their supportive function on epithelial progenitors towards an inhibitory one in an organoid assay. These results imply that chronic inflammation functions as a shift towards inhibition of repair, thereby contributing to chronic inflammatory diseases like COPD.