Advances on the role of lung macrophages in the pathogenesis of chronic obstructive pulmonary disease in the Era of Single-Cell Genomics

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous respiratory disorder characterized by persistent airflow limitation. The diverse pathogenic mechanisms underlying COPD progression remain incompletely understood. Macrophages, serving as the most representative immune cells in the respiratory tract, constitute the first line of innate immune defense and maintain pulmonary immunological homeostasis. Recent advances have provided deeper insights into the phenotypic and functional alterations of pulmonary macrophages and their role in COPD pathogenesis. Notably, the advent of single-cell RNA sequencing has revolutionized our understanding of macrophage molecular heterogeneity in COPD. Herein, we review principal investigations concerning the sophisticated mechanisms through which pulmonary macrophages influence COPD, encompassing inflammatory mediator production, protease/antiprotease release, and phagocytic activity. Additionally, we synthesize findings from available literature regarding all identified pulmonary macrophage sub-populations in COPD, thereby advancing our comprehension of macrophage heterogeneity's significance in the complex pathophysiological mechanisms of COPD.