Airway epithelial cell–lung macrophage crosstalk in type 2-high and low asthma endotypes: mechanisms and therapeutic strategies

Abstract

Asthma is a heterogeneous chronic airway disease. Asthma endotypes are mainly classified as type 2-high and type 2-low, based on immunological and molecular mechanisms, providing a more comprehensive framework for understanding the underlying pathological processes. Airway epithelial cells (AECs) and lung macrophages contribute to airway homeostasis and asthmatic inflammation through communication that can support either tissue protection or disease-associated responses. This narrative review integrates their physiological and pathological functions, focusing on AEC-to-macrophage and macrophage-to-AEC signaling within broader multicellular networks across different asthma endotypes. Direct functional evidence for intercellular communication from associations and indirect mechanisms is distinguished and graded. Therapeutic strategies targeting AECs, lung macrophages, and their crosstalk, including both clinically validated and preclinical approaches, are also discussed. The AEC–macrophage axis exhibits context-dependent signaling that may amplify inflammation or support protective regulation, providing a basis for evaluating potential therapeutic interventions.