Multi-level immune response network in mild-moderate Chronic Obstructive Pulmonary Disease (COPD)

Area of Science:

• Pulmonary immunology
• Transcriptomics
• Systems biology

Background:

• Chronic Obstructive Pulmonary Disease (COPD) involves abnormal immune responses to smoking.
• The relationship between lung and systemic immunity, lung transcriptome changes, and the impact of smoking vs. disease presence remain unclear.

Purpose of the Study:

• To investigate immune cell composition in lung tissue and blood.
• To analyze the influence of lung immune infiltrate on the lung transcriptome.
• To differentiate the roles of active smoking and disease presence.

Main Methods:

• Simultaneous collection of lung tissue and blood from 65 individuals.
• Flow cytometry for immune cell profiling.
• Whole lung transcriptome analysis and Weighted Gene Co-expression Network Analysis (WGCNA).

Main Results:

• Current smoking and COPD independently reduced lung T cells and increased specific macrophages (CD80+CD163+).
• Immune cell changes, smoking status, and airflow limitation correlated with WGCNA modules enriched in iron transport, extracellular matrix, and cilium organization genes.
• Circulating white blood cell counts correlated with lung macrophages and T cells.

Conclusions:

• Mild-to-moderate COPD lung immune infiltrate is linked to active smoking and disease presence.
• These immune changes correlate with alterations in the whole lung transcriptome.
• Systemic immune changes in blood marginally reflect lung tissue alterations.