Division of Pulmonary and Critical Care Medicine.
Harvard Medical School, Boston, Massachusetts.
Am J Respir Crit Care Med. 2023 Dec 1;208(11):1177-1195. doi: 10.1164/rccm.202305-0924OC.
Despite the importance of inflammation in chronic obstructive pulmonary disease (COPD), the immune cell landscape in the lung tissue of patients with mild-moderate disease has not been well characterized at the single-cell and molecular level. To define the immune cell landscape in lung tissue from patients with mild-moderate COPD at single-cell resolution. We performed single-cell transcriptomic, proteomic, and T-cell receptor repertoire analyses on lung tissue from patients with mild-moderate COPD ( = 5, Global Initiative for Chronic Obstructive Lung Disease I or II), emphysema without airflow obstruction ( = 5), end-stage COPD ( = 2), control ( = 6), or donors ( = 4). We validated in an independent patient cohort ( = 929) and integrated with the murine model of COPD. Mild-moderate COPD lungs have increased abundance of two CD8 T cell subpopulations: cytotoxic KLRG1TIGITCX3CR1 TEMRA (T effector memory CD45RA) cells, and DNAM-1CCR5 T resident memory (T) cells. These CD8 T cells interact with myeloid and alveolar type II cells via and have hyperexpanded T-cell receptor clonotypes. In an independent cohort, the CD8KLRG1 TEMRA cells are increased in mild-moderate COPD lung compared with control or end-stage COPD lung. Human CD8KLRG1 TEMRA cells are similar to CD8 T cells driving inflammation in an aging-related murine model of COPD. CD8 TEMRA cells are increased in mild-moderate COPD lung and may contribute to inflammation that precedes severe disease. Further study of these CD8 T cells may have therapeutic implications for preventing severe COPD.
尽管炎症在慢性阻塞性肺疾病(COPD)中很重要,但轻度至中度疾病患者肺部组织中的免疫细胞景观在单细胞和分子水平上尚未得到很好的描述。为了在单细胞分辨率下定义轻度至中度 COPD 患者肺部组织中的免疫细胞景观,我们对轻度至中度 COPD 患者(n=5,GOLD 分期 I 或 II)、无气流阻塞性肺气肿(n=5)、终末期 COPD(n=2)、对照(n=6)或供体(n=4)的肺组织进行了单细胞转录组学、蛋白质组学和 T 细胞受体库分析。我们在独立的患者队列(n=929)中进行了验证,并与 COPD 的小鼠模型进行了整合。轻度至中度 COPD 肺中增加了两种 CD8+T 细胞亚群的丰度:细胞毒性 KLRG1+TIGIT+CX3CR1+TEMRA(T 效应记忆 CD45RA)细胞和 DNAM-1+CCR5+T 驻留记忆(T)细胞。这些 CD8+T 细胞通过与髓样细胞和肺泡 II 型细胞相互作用,并具有超扩展的 T 细胞受体克隆型。在一个独立的队列中,与对照或终末期 COPD 肺相比,轻度至中度 COPD 肺中的 CD8+KLRG1+TEMRA 细胞增加。人类 CD8+KLRG1+TEMRA 细胞与在衰老相关的 COPD 小鼠模型中驱动炎症的 CD8+T 细胞相似。轻度至中度 COPD 肺中 CD8+TEMRA 细胞增加,可能导致严重疾病之前的炎症。对这些 CD8+T 细胞的进一步研究可能对预防严重 COPD 具有治疗意义。
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