Interactions via α₂β₁ Cell Integrin May Protect against the Progression of Airway Structural Changes in Asthma

Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of β₁-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α₂ integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α₁ and α₂ integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α₂ integrin chain. Expression of α₂β₁ integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α₂β₁ integrin on blood and airway CD8⁺ T-cells. Thicker airway walls in CT were associated with lower α₂ integrin chain on blood CD4⁺ T-cells and airway eosinophils. Our data suggest that α₂β₁ integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.