Evidence for Interleukin-17C governing interleukin-17A pathogenicity and promoting asthma endotype switching in bronchiectasis.
Summary
In BAO, circulating IL-17C correlates with IL-17A and ILC3s. In a chronic P. aeruginosa plus OVA model, IL-17C drives IL-17A via IL-17RE on ILC3s, shifting asthma toward a neutrophilic phenotype; genetic Il17re ablation attenuates this switch. Epithelial barrier disruption is linked to IL-17C production, nominating IL-17C as a therapeutic target.
Key Findings
- IL-17C levels positively correlated with IL-17A and ILC3s in BAO patient blood.
- In a chronic P. aeruginosa + OVA mouse model, IL-17C amplified IL-17A via IL-17RE on ILC3s, promoting neutrophilic asthma endotype switching.
- Il17re ablation attenuated ILC3 responses and IL-17A-mediated endotype switching; epithelial barrier disruption associated with IL-17C production.
Clinical Implications
IL-17C may serve as a biomarker and therapeutic target in bronchiectasis-asthma overlap, particularly in patients with chronic Pseudomonas infection and neutrophilic inflammation.
Why It Matters
This work provides mechanistic evidence connecting IL-17C to IL-17A-driven neutrophilic asthma in bronchiectasis, explaining endotype switching and highlighting a druggable cytokine axis.
Limitations
- Sample size and multicenter validation were not detailed.
- Translational relevance needs clinical trials to test IL-17C-targeted interventions.
Future Directions
Prospective studies to validate IL-17C as a biomarker in BAO and early-phase trials of IL-17C/IL-17RE pathway inhibitors in neutrophilic asthma endotypes.
Study Information
- Study Type
- Case series
- Research Domain
- Pathophysiology
- Evidence Level
- IV - Preclinical mechanistic study with human observational correlations and mouse models
- Study Design
- OTHER