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

## TL;DR

CD207-positive dendritic cells worsen COPD by activating CD8+ T cells, offering a new treatment target for emphysema.

## Contribution

CD207+ dendritic cells are identified as key drivers of emphysema via CD8+ T cell activation in COPD.

## Key findings

- CD207+ DCs correlate with emphysema severity and lung function decline in COPD patients.
- CD207+ DCs promote CD8+ T cell proliferation via MHC-I antigen cross-presentation.
- Cigarette smoke-induced GM-CSF drives expansion of CD207+ DCs in COPD.

## 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 (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.

CD207+ dendritic cells (DCs) drive emphysema by promoting CD8⁺ T cell cytotoxicity via Birbeck granule‐dependent MHC‐I antigen presentation. This DC subset is expanded by cigarette smoke‐induced oxidative stress, which triggers granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) release from airway epithelium. Targeting the CD207⁺ DC‐CD8⁺ T cell axis therefore represents a promising therapeutic strategy for chronic obstructive pulmonary disease (COPD).