Dynamic Changes of Immune Cells and Therapeutic Responses in Experimental Models of COPD

Jingxian Xie^1,2*Pengfei Li¹Jianjun Du²Shiran Li¹Zhimin Li¹JIAO ZHANG¹Siyu Zeng¹Yanqiu zhang¹Yong Yang^1*

• ¹Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China
• ²Southwest Medical University, Luzhou, China

Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory disorder characterized by a complex pathogenesis involving chronic inflammation, protease–antiprotease imbalance, oxidative stress, and epigenetic regulation. Experimental models, including cigarette smoke exposure, air pollution, and acute exacerbation models, provide essential platforms for investigating immune cell dynamics during disease initiation and progression. Macrophages contribute to inflammatory amplification and tissue destruction through polarization imbalance and metabolic reprogramming. Neutrophils exacerbate persistent lung injury via recruitment, protease release, NET formation, and delayed apoptosis, while also promoting airway remodeling during the repair phase. T cells—particularly CD8⁺, Th1/Th17, and tissue-resident memory T cells—sustain chronic inflammation through cytotoxicity and cytokine networks, whereas impaired Treg function hinders inflammation resolution. Additional immune populations, such as NK cells, eosinophils, and fibrocytes, further drive inflammatory amplification and fibrotic remodeling. Therapeutic explorations targeting distinct inflammatory phenotypes indicate that conventional glucocorticoids and PDE4 inhibitors remain beneficial in eosinophil-driven inflammation, whereas biologics targeting IL-5, IL-13/IL-4, TSLP, and IL-33 have produced variable outcomes in COPD clinical trials. These findings highlight the importance of precision phenotyping and personalized immunomodulatory strategies. Overall, systematic elucidation of immune cell dynamics in COPD experimental models provides new insights into mechanisms of inflammation persistence and therapeutic responses, offering a theoretical basis for developing targeted interventions.