Airway epithelial inflammatory pathways

The airway epithelium serves as a critical interface between the host and the environment, functioning as both a physical barrier and an active orchestrator of inflammatory responses [1, 9]. Upon exposure to environmental triggers such as allergens, viruses, and pollutants, airway epithelial cells release upstream cytokines known as alarmins, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25) [4, 8]. These alarmins initiate complex inflammatory pathways, primarily the Type 2 (T2) immune response involving ILC2s, Th2 cells, and eosinophils, which drive the pathophysiology of chronic respiratory diseases like asthma and COPD [1, 11]. Dysregulation of these pathways leads to persistent inflammation, airway hyperresponsiveness, mucus hypersecretion, and structural remodeling [2, 5]. Therapeutic strategies targeting these pathways, such as the anti-TSLP monoclonal antibody tezepelumab, aim to intercept the inflammatory cascade at its source, providing clinical benefits across various asthma phenotypes, including those with low T2 biomarkers [8, 9].

Other names

Epithelial-immune crosstalkEpithelial alarmin signalingAirway epithelial signaling pathwaysEpithelial-derived alarmin pathways

Inhibition of epithelial-derived alarmins (TSLP, IL-33, IL-25) or their receptors (ST2, IL-4Rα) to suppress upstream inflammatory signaling and downstream Type 2 immune responses [4, 8, 12].