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

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 (FEV₁%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.