Increased expression of Clec9A on cDC1s associated with cytotoxic CD8+ T cell response in COPD

Abstract

Although C-type lectin domain family 9A (Clec9A) on conventional type 1 dendritic cells (cDC1s) plays a critical role in cytotoxic CD8⁺ T cell response in cancers and viral infections, its role in chronic obstructive pulmonary disease (COPD) is unknown. We measured the expression of Clec9A in sera, bronchoalveolar lavage fluid (BALF), and peripheral blood mononuclear cells (PBMCs) from controls and COPD patients. The percentages of Clec9A⁺ DC and cytotoxic CD8⁺ T cell in the BALF were determined by flow cytometry between patients with COPD and non-obstructive chronic bronchitis (NOCB). Compared with healthy individuals, the serum levels of Clec9A were increased at different stages of COPD patients, and the mRNA and protein levels of Clec9A were both increased in COPD patients at GOLD stages III-IV. The percentage of Clec9A⁺ DCs was also increased in the BALF of COPD patients compared with NOCB patients. Moreover, enhanced Clec9A⁺ DCs recruitment was positively correlated with cytotoxic CD8⁺ T cell response in the BALF of COPD patients. This study suggests that Clec9A⁺ DCs participate in the CD8⁺ T cell-mediated chronic airway inflammation in COPD.

Keywords: C-type lectin domain family 9A; Chronic obstructive pulmonary disease; Conventional type 1 dendritic cells; Cytotoxic CD8(+) T lymphocyte; Filamentous actin.