Interleukin-1 receptor and caspase-1 are required for the Th17 response in nitrogen dioxide-promoted allergic airway disease

Rebecca A. Martin, Jennifer L. Ather, Lennart K.A. Lundblad, Benjamin T. Suratt, Jonathan E. Boyson, Ralph C. Budd, John F. Alcorn, Richard A. Flavell, Stephanie C. Eisenbarth, Matthew E. Poynter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Nitrogen dioxide (NO2) is an environmental pollutant and endogenously generated oxidant associated with the development, severity,andexacerbationofasthma.NO2 exposure is capableofallergically sensitizing mice to the innocuous inhaled antigen ovalbumin (OVA),promotingneutrophilandeosinophil recruitment,andamixed Th2/Th17 response upon antigen challenge that is reminiscent of severeasthma. However, the identityof IL-17A-producingcells and the mechanisms governing their ontogeny in NO2-promoted allergic airway disease remain unstudied. We measured the kinetics of lunginflammation after antigen challenge inNO 2-promoted allergic airway disease, including inflammatory cells in bronchoalveolar lavage and antigen-specific IL-17A production from the lung. We determined that IL-17A+ cells were predominately CD4+T cell receptor (TCR)β+ Th17 cells, and that a functional IL-1 receptor was required for Th17, but not Th2, cytokine production after in vitro antigen restimulation of lung cells. The absence of natural killer T cells, γδ T cells, or the inflammasome scaffold nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain (Nlrp)3 did not affect the development of NO2-promoted allergic inflammation or IL-17A production. Similarly, neutrophil depletion or the neutralization of IL-1α during sensitization exerted no effect on these parameters. However, the absence of caspase-1 significantly reduced IL-17A production from lung cells without affecting Th2 cytokines or lung inflammation. Finally, the intranasal administration of IL-1β and the inhalation of antigen promoted allergic sensitization that was reflected by neutrophilic airway inflammation and IL-17A production from CD4+TCRβ+ Th17 cells subsequent to antigen challenge. Thesedataimplicatearolefor caspase-1andIL- 1βintheIL-1receptor- dependent Th17 response manifest in NO 2-promoted allergic airway disease.

Original languageEnglish (US)
Pages (from-to)655-664
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume48
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

Keywords

  • Asthma
  • IL-17
  • IL-1R
  • Nitrogen dioxide
  • Th17

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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