IL-1 and IL-23 Mediate Early IL-17A Production in Pulmonary Inflammation Leading to Late Fibrosis
Author Information
Author(s): Gasse Paméla, Riteau Nicolas, Vacher Rachel, Michel Marie-Laure, Fautrel Alain, di Padova Franco, Fick Lizette, Charron Sabine, Lagente Vincent, Eberl Gérard, Le Bert Marc, Quesniaux Valérie F. J., Huaux François, Leite-de-Moraes Maria, Ryffel Bernhard, Couillin Isabelle
Primary Institution: University of Orleans and CNRS, UMR6218, Orleans, France
Hypothesis
IL-1β secreted upon lung injury may induce innate IL-23 and IL-17 expression in lung resulting in pulmonary inflammation and evolution to fibrosis.
Conclusion
The study demonstrates that an early IL-1β-IL-23-IL-17A axis is essential for pulmonary inflammation and fibrosis.
Supporting Evidence
- IL-1β and IL-23 were shown to induce innate IL-17 production from γδ T cells.
- IL-17A, but not IL-17F, is essential for bleomycin-induced acute lung inflammation.
- IL-23p19 and IL-17A are upstream of TGF-β1, the central mediator of lung fibrosis.
- Neutrophil recruitment and TIMP-1 expression were reduced in IL-23p19 deficient mice.
- Blocking IL-17A significantly reduced neutrophil recruitment and pro-inflammatory cytokine levels.
Takeaway
When the lungs are injured, certain signals make the body produce substances that cause inflammation and scarring, which can lead to serious lung problems.
Methodology
The study used a bleomycin model in deficient mice to assess the role of IL-23 and IL-17 in pulmonary inflammation and fibrosis.
Statistical Information
P-Value
<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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