Lung epithelial cells: Upstream targets in type 2-high asthma

Area of Science:

• Immunology
• Pulmonology
• Epithelial Biology

Background:

• Asthma is classified into type 2-high and type 2-low endotypes based on distinct molecular mechanisms.
• The lung epithelium, previously viewed as a barrier, is now recognized as a critical component of the innate immune system in asthma.
• Epithelial cells actively respond to environmental triggers like allergens and microbes, influencing immune cell activation.

Purpose of the Study:

• To review the role of the lung epithelium in the development of type 2-high asthma.
• To discuss epithelial responses to viral infections (rhinovirus, RSV, SARS-CoV-2) and their impact on asthma.
• To summarize clinical trial outcomes for biologicals targeting epithelial-derived cytokines in asthma.

Main Methods:

• Review of murine models and human studies on epithelial contributions to type 2-high asthma.
• Analysis of epithelial cell responses to allergens and respiratory viruses.
• Summary of clinical trial data for targeted biological therapies.

Main Results:

• The epithelium actively contributes to Th2 sensitization and the development of type 2-high asthma.
• Epithelial responses to viruses like rhinovirus, RSV, and SARS-CoV-2 influence asthma development and exacerbations.
• Clinical trials targeting epithelial-derived cytokines show promising results for asthma treatment.

Conclusions:

• The lung epithelium is a central orchestrator in type 2-high asthma pathogenesis.
• Understanding epithelial responses to environmental triggers is crucial for asthma management.
• Targeting epithelial-derived cytokines represents a promising therapeutic strategy for asthma.