Endothelial Sox17 promotes allergic airway inflammation

Area of Science:

• Immunology
• Molecular Biology
• Respiratory Medicine

Background:

• Interleukin-33 (IL-33) is elevated in eosinophilic asthma and is a potential therapeutic target.
• IL-33 activates endothelial cells, leading to the upregulation of Sry-related high-mobility-group box (Sox) 17, an endothelium-specific transcription factor.

Purpose of the Study:

• To investigate the relationship between Sox17 and IL-33.
• To explore the role of Sox17 in asthma pathogenesis using a mouse model.

Main Methods:

• Ovalbumin (OVA) challenge in mice to induce airway inflammation.
• Utilized endothelium-specific Sox17 null mutant mice.
• Administered IL-33 neutralizing antibody to assess IL-33 and Sox17 interplay.
• Conducted in vitro experiments on human endothelial cells.

Main Results:

• IL-33 and Sox17 levels increased in OVA-challenged mouse lungs.
• Anti-IL-33 treatment reduced airway inflammation and Sox17 expression.
• Endothelial Sox17 deletion significantly ameliorated asthma features, including inflammation and hyperresponsiveness.
• Sox17 deletion decreased lung monocyte and dendritic cell populations.
• Sox17 positively correlated with CCL2 and ICAM-1 in IL-33-stimulated endothelial cells, promoting monocyte adhesion.

Conclusions:

• IL-33 regulates Sox17, and Sox17 genetic ablation in endothelial cells alleviates asthma pathophysiology.
• Sox17 represents a potential therapeutic target for asthma management.