慢性阻塞性肺病
CD8型
医学
免疫学
细胞毒性T细胞
免疫系统
肺
炎症
T细胞
生物
内科学
生物化学
体外
作者
Ana B. Villaseñor-Altamirano,Dhawal Jain,Yunju Jeong,Jaivardhan A Menon,Mamoru Kamiya,Hibah Haider,Reshmi Manandhar,Muhammad Dawood Amir Sheikh,Humra Athar,Louis T Merriam,Min Hyung Ryu,Takanori Sasaki,Peter J. Castaldi,Deepak A. Rao,Lynette M. Sholl,Marina Vivero,Craig P. Hersh,Xiaobo Zhou,Justus Veerkamp,Jeong Yun,Edy Y. Kim
标识
DOI:10.1164/rccm.202305-0924oc
摘要
Rationale: 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. Objectives: To define the immune cell landscape in lung tissue from patients with mild-moderate COPD at single-cell resolution. Methods: We performed single-cell transcriptomic, proteomic, and T-cell receptor repertoire analyses on lung tissue from patients with mild-moderate COPD (n = 5, Global Initiative for Chronic Obstructive Lung Disease I or II), emphysema without airflow obstruction (n = 5), end-stage COPD (n = 2), control (n = 6), or donors (n = 4). We validated in an independent patient cohort (N = 929) and integrated with the Hhip+/− murine model of COPD. Measurements and Main Results: Mild-moderate COPD lungs have increased abundance of two CD8+ T cell subpopulations: cytotoxic KLRG1+TIGIT+CX3CR1+ TEMRA (T effector memory CD45RA+) cells, and DNAM-1+CCR5+ T resident memory (TRM) cells. These CD8+ T cells interact with myeloid and alveolar type II cells via IFNG and have hyperexpanded T-cell receptor clonotypes. In an independent cohort, the CD8+KLRG1+ TEMRA cells are increased in mild-moderate COPD lung compared with control or end-stage COPD lung. Human CD8+KLRG1+ TEMRA cells are similar to CD8+ T cells driving inflammation in an aging-related murine model of COPD. Conclusions: 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.
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