Investigating COPD Pathogenesis: Abnormal Iron Homeostasis in Alveolar Macrophages

Disruptions in iron metabolism within alveolar macrophages may play a key role in the progression and exacerbation of chronic obstructive pulmonary disease (COPD), according to ongoing research led by William Zhang, MD, Assistant Professor of Medicine at Weill Cornell Medicine. His research aims to better understand the biological mechanisms underlying COPD and address gaps that currently limit the development of targeted therapies.

Zhang spoke in the third issue of The Respiratory Report, a quarterly newsletter from HCPLive that is powered by the American Lung Association Research Institute, on his team’s current research in this area.

Zhang and his team used murine models of cigarette smoke exposure and single-cell RNA sequencing to investigate how dysregulated iron metabolism in alveolar macrophages contributes to COPD pathogenesis and exacerbation risk. He found that cigarette smoke induces iron loading in these immune cells, impairing their function, and that disrupting iron regulation may reduce emphysema development but could also weaken infection response. He also discussed proof-of-concept studies in humans the team is conducting.

"To get rid of an important protein that breaks down ferritin and allows the cell to retrieve iron when it needs to, especially when macrophages are fighting infection, I think probably also hampers them to some extent in this infection model. So, I think that the biology behind this is is more complex than we initially hypothesized and not so straightforward," Zhang said.

To learn more about Zhang's research, view the interview above or read his contribution to the third issue of The Respiratory Report here:

Abnormal Iron Homeostasis in Alveolar Macrophages: Implications for COPD Pathogenesis