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Airway epithelial cell and lung macrophage crosstalk provides a basis for targeting asthma endotypesLung Cell Communication May Influence Asthma Inflammation Levels

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Key Takeaway
Note that the AEC-macrophage axis provides a potential basis for developing targeted therapies for various asthma endotypes.

This narrative review explores the complex signaling between airway epithelial cells (AEC) and lung macrophages in the context of asthma. The review focuses on the AEC-macrophage axis, highlighting how these interactions can lead to either pro-inflammatory responses or protective regulatory mechanisms depending on the specific context.

The authors synthesize findings regarding AEC-to-macrophage and macrophage-to-AEC signaling. They suggest that these interactions are critical for determining the inflammatory environment. The review identifies several potential therapeutic strategies targeting AECs, lung macrophages, and their mutual crosstalk as avenues for treating different asthma endotypes.

While the review provides a theoretical basis for new interventions, it distinguishes between direct functional evidence and indirect mechanisms. Some therapeutic strategies discussed are preclinical rather than clinically validated. The review serves as a conceptual framework for future drug development and does not provide specific clinical trial data or safety outcomes.

How this fits prior evidence

This narrative review addresses a gap in understanding the cellular mechanisms of asthma by focusing on the AEC-macrophage axis. While prior coverage has identified specific treatments like depemokimab for eosinophilic asthma and FF/UMEC/VI for clinical remission, this review focuses on the underlying cellular crosstalk. It does not relate to the findings regarding H. pylori, CAR-engineered cell therapy, piRNA biomarkers, or depemokimab.

This review looked at how airway epithelial cells (AEC) and lung macrophages communicate with each other. These two types of cells are very important for lung health. The study found that this communication, known as the AEC-macrophage axis, can act in different ways depending on the situation. In some cases, it might increase inflammation, while in other cases, it might help regulate and protect the lungs.

Because these cells interact in complex ways, they provide a target for future treatments. The research suggests that focusing on these specific cell signals could help doctors develop better ways to manage different types of asthma.

It is important to note that this is a narrative review of existing information. Some of the methods discussed are still in the early stages of research and have not been fully tested in humans yet. This information is for educational purposes and does not replace a doctor's advice.

What this means for you:
Cell communication in the lungs may play a role in asthma, offering a potential path for future treatments.

Common questions

What is the role of lung cells in asthma?

Airway epithelial cells and lung macrophages communicate with each other to manage lung health. This interaction, called the AEC-macrophage axis, can either increase inflammation or provide protective regulation. Understanding these signals helps researchers identify ways to target specific types of asthma.

How does this research help with asthma treatment?

The review identifies the cell communication as a potential target for new therapies. By focusing on the signals between these cells, scientists hope to develop more specific treatments for different asthma types. However, many of these strategies are still in the preclinical stages.

Study Details

Study typeSystematic review
EvidenceLevel 1
PublishedOct 2026
View Original 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.
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