Blood neutrophils in COPD derive from activated progenitors in the bone marrow

Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small airway inflammation, emphysema and severe breathing difficulties. Low-grade systemic inflammation is an established hallmark of severe disease, however, the molecular changes in peripheral immune cells remain far from understood. We combined multi-color flow cytometry with single-cell RNA sequencing and showed that blood neutrophil numbers are significantly increased in COPD and they are a heterogeneous population. A transcriptomic state that expressed interferon response genes correlated with alveolar damage and acute exacerbations. Furthermore, bronchoalveolar neutrophils expressed gene signatures corresponding to certain blood neutrophil states. Last, our data in a murine model of cigarette smoke exposure demonstrated that bone marrow neutrophil progenitors are expanded in smoke-treated animals and display signs of immune activation. Our study provides evidence that COPD systemic inflammation may derive from an activated haematopoietic precursor compartment.

慢性阻塞性肺疾病（COPD）是一种以小气道炎症、肺气肿和严重呼吸困难为特征的呼吸系统疾病。低度全身性炎症是重症疾病的明确标志，然而，外周免疫细胞的分子变化仍远未得到充分理解。我们结合多色流式细胞术与单细胞RNA测序技术，发现COPD患者血液中性粒细胞数量显著增加，且其为一个异质性群体。表达干扰素反应基因的转录组状态与肺泡损伤和急性加重相关。此外，支气管肺泡中性粒细胞表达与特定血液中性粒细胞状态相对应的基因特征。最后，我们的数据在香烟烟雾暴露的小鼠模型中表明，经烟雾处理的动物骨髓中性粒细胞祖细胞扩增，并表现出免疫激活的迹象。本研究提供了证据，表明COPD的全身性炎症可能源自激活的造血祖细胞区室。