Abstract
The airway epithelium is exposed to numerous external irritants including infectious agents, environmental allergens, and atmospheric pollutants, releasing epithelial cytokines including thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 and initiating downstream type 2 (IL-4, IL-13, and IL-5) and IgE-driven pathways. These pathways trigger the initiation and progression of allergic airway diseases, including chronic rhinosinusitis with nasal polyps (CRSwNP), allergic rhinitis (AR), and allergic asthma. However, the use of biological agents that target downstream cytokines, such as IL-5, IL-4, and IL-13 receptors and IgE, might not be sufficient to manage some patients successfully. Instead of blocking downstream cytokines, targeting upstream epithelial cytokines has been proposed to address the complex immunologic networks associated with allergic airway diseases. Osteopontin (OPN), an extracellular matrix glyco-phosphoprotein, is a key mediator involved in Th1-related diseases, including systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Emerging evidence, including ours, indicates that epithelial-cell-derived OPN also plays an essential role in Th2-skewed airway diseases, including CRSwNP, AR, and allergic asthma involving the Th17 response. Therefore, we reviewed the current knowledge of epithelial-cell-derived OPN in the pathogenesis of three type-2-biased airway diseases and provided a direction for its future investigation and clinical relevance.