Pulmonary fibrosis is a progressive and debilitating lung disease characterized by the excessive accumulation of extracellular matrix (ECM) components within the lung parenchyma. However, the underlying mechanism remains largely elusive, and the treatment options available for pulmonary fibrosis are limited. Interleukin 5 receptor, alpha (IL5RA) is a well-established regulator of eosinophil activation, involved in eosinophil-mediated anti-parasitic activities and allergic reactions. Recent studies have indicated additional roles of IL5RA in lung epithelium and fibroblasts. Nevertheless, its involvement in pulmonary fibrosis remains unclear. In present study, we employed single-cell analyses alongside molecular and cellular assays to unveil the expression of IL5RA in lung epithelial cells. Moreover, using both and models, we demonstrated a notable upregulation of epithelial IL5RA during the progression of pulmonary fibrosis. This upregulated IL5RA expression subsequently promotes epithelial-mesenchymal transition (EMT), leading to the generation of mesenchymal phenotype with augmented capability for ECM production. Importantly, our findings uncovered that the pro-fibrotic function of IL5RA is mediated by Jak2/STAT3 signaling cascades. Inhibiting IL5RA has the potential to deactivate Jak2/STAT3 and suppress the downstream EMT process and ECM production, thereby offering a promising therapeutic strategy for pulmonary fibrosis.

中文翻译：

---

上皮IL5RA通过Jak2/STAT3级联促进肺纤维化中的上皮-间质转化

肺纤维化是一种进行性、使人衰弱的肺部疾病，其特征是肺实质内细胞外基质（ECM）成分过度积累。然而，潜在的机制在很大程度上仍然难以捉摸，并且肺纤维化可用的治疗选择也很有限。白细胞介素 5 受体 α (IL5RA) 是一种成熟的嗜酸性粒细胞活化调节剂，参与嗜酸性粒细胞介导的抗寄生虫活性和过敏反应。最近的研究表明 IL5RA 在肺上皮和成纤维细胞中具有其他作用。然而，其与肺纤维化的关系仍不清楚。在本研究中，我们采用单细胞分析以及分子和细胞测定来揭示肺上皮细胞中 IL5RA 的表达。此外，使用 和 模型，我们证明了肺纤维化进展过程中上皮 IL5RA 的显着上调。这种上调的 IL5RA 表达随后促进上皮-间质转化 (EMT)，导致产生具有增强的 ECM 产生能力的间质表型。重要的是，我们的研究结果发现 IL5RA 的促纤维化功能是由 Jak2/STAT3 信号级联介导的。抑制 IL5RA 有可能使 Jak2/STAT3 失活并抑制下游 EMT 过程和 ECM 产生，从而为肺纤维化提供有前景的治疗策略。