CD207-Positive Dendritic Cells Promote Emphysema Through CD8T 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 (CD207DCs) as pivotal mediators of emphysema progression. In patients with COPD, the abundance of CD207DCs in small airways correlates with both emphysema severity and lung function decline (FEV%pred). In a murine emphysema model, adoptive transfer of CD207DCs reversed the attenuation of emphysema, inflammation and CD8T-cell expansion in CD207-knockout mice. Mechanistically, cigarette smoke-induced epithelial GM-CSF drives the expansion of CD207DCs. Upon activation by damage-associated molecular patterns (DAMPs), these DCs promote CD8T cell proliferation and activation via Birbeck granule-mediated MHC-I antigen cross-presentation. Collectively, these findings demonstrate that CD207DCs orchestrate a pathogenic CD8T-cell response in emphysema and represent a promising therapeutic target.