CD207‐Positive Dendritic Cells Promote Emphysema Through CD8 + T Cell Pathway in Chronic Obstructive Pulmonary Disease

ABSTRACT Emphysema remains a major challenge in the management of chronic obstructive pulmonary disease (COPD). This study identifies CD207‐positive dendritic cells (CD207 + DCs) as pivotal mediators of emphysema progression. In patients with COPD, the abundance of CD207 + DCs in small airways correlates with both emphysema severity and lung function decline (FEV 1 %pred). In a murine emphysema model, adoptive transfer of CD207 + DCs reversed the attenuation of emphysema, inflammation and CD8 + T‐cell expansion in CD207 ‐knockout mice. Mechanistically, cigarette smoke‐induced epithelial GM‐CSF drives the expansion of CD207 + DCs. Upon activation by damage‐associated molecular patterns (DAMPs), these DCs promote CD8 + T cell proliferation and activation via Birbeck granule‐mediated MHC‐I antigen cross‐presentation. Collectively, these findings demonstrate that CD207 + DCs orchestrate a pathogenic CD8 + T‐cell response in emphysema and represent a promising therapeutic target.