Eosinophils promote lung emphysema via CTSL. Eosinophils promote lung emphysema via CTSL

Patients with chronic obstructive pulmonary disease (COPD) having higher blood eosinophil levels exhibit worse lung function and more severe emphysema, implying the potential role of eosinophils in emphysema development. However, the specific mechanism underlying eosinophil-mediated emphysema development is not fully elucidated. In this study, single-cell RNA sequencing was used to identify eosinophil subgroups in mouse models of asthma and emphysema and analyze their functions. Analysis of the accumulated eosinophils revealed differential transcriptomes between the mouse lungs of elastase-induced emphysema and ovalbumin-induced asthma., Eosinophil depletion alleviated elastase-induced emphysema. Notably, eosinophil-derived cathepsin L (CTSL) degraded the extracellular matrix (ECM), causing emphysema in the pulmonary tissue. Eosinophils were positively correlated with serum CTSL levels, which were increased in patients with emphysema than in those without emphysema. Collectively, these results suggest that CTSL expression in eosinophils plays an important role in ECM degradation and remodeling and is related to emphysema in patients with COPD. Therefore, eosinophil-derived CTSL may serve as a potential therapeutic target for patients with emphysema. Overall design: 13 sample from lung tissue

血液嗜酸性粒细胞水平升高的慢性阻塞性肺疾病（COPD）患者，肺功能更差且肺气肿程度更为严重，提示嗜酸性粒细胞可能在肺气肿的发生发展过程中发挥潜在作用。然而，嗜酸性粒细胞介导的肺气肿发生的具体机制尚未完全阐明。本研究采用单细胞RNA测序（single-cell RNA sequencing）技术，在哮喘与肺气肿小鼠模型中鉴定嗜酸性粒细胞亚群并分析其功能。对累积的嗜酸性粒细胞进行分析后发现，弹性蛋白酶诱导的肺气肿小鼠肺部与卵清蛋白诱导的哮喘小鼠肺部的转录组存在显著差异。嗜酸性粒细胞清除可缓解弹性蛋白酶诱导的肺气肿。值得注意的是，嗜酸性粒细胞来源的组织蛋白酶L（cathepsin L, CTSL）可降解细胞外基质（extracellular matrix, ECM），进而导致肺组织出现肺气肿病变。嗜酸性粒细胞与血清CTSL水平呈正相关，且肺气肿患者的血清CTSL水平高于非肺气肿患者。综上，本研究结果表明，嗜酸性粒细胞中的CTSL表达在细胞外基质的降解与重塑过程中发挥重要作用，且与COPD患者的肺气肿病变密切相关。因此，嗜酸性粒细胞来源的CTSL有望成为肺气肿患者的潜在治疗靶点。整体实验设计：共纳入13份肺组织样本。