IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways Academic Article uri icon

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abstract

  • RATIONALE: IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma. OBJECTIVES: The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the role of IL-9 in acute inflammatory models; here we have investigated the effects of IL-9 blockade during chronic allergic inflammation. METHODS: Mice were exposed to either prolonged ovalbumin or house dust mite allergen challenge to induce chronic inflammation and airway remodeling. MEASUREMENTS AND MAIN RESULTS: We found that IL-9 governs allergen-induced mast cell (MC) numbers in the lung and has pronounced effects on chronic allergic inflammation. Anti-IL-9 antibody-treated mice were protected from airway remodeling with a concomitant reduction in mature MC numbers and activation, in addition to decreased expression of the profibrotic mediators transforming growth factor-β1, vascular endothelial growth factor, and fibroblast growth factor-2 in the lung. Airway remodeling was associated with impaired lung function in the peripheral airways and this was reversed by IL-9 neutralization. In human asthmatic lung tissue, we identified MCs as the main IL-9 receptor expressing population and found them to be sources of vascular endothelial growth factor and fibroblast growth factor-2. CONCLUSIONS: Our data suggest an important role for an IL-9-MC axis in the pathology associated with chronic asthma and demonstrate that an impact on this axis could lead to a reduction in chronic inflammation and improved lung function in patients with asthma.

authors

  • Kearley, Jennifer
  • Erjefalt, Jonas S
  • Andersson, Cecilia
  • Benjamin, Ebony
  • Jones, Carla P
  • Robichaud, Annette
  • Pegorier, Sophie
  • Brewah, Yambasu
  • Burwell, Timothy J
  • Bjermer, Leif
  • Kiener, Peter A
  • Kolbeck, Roland
  • Lloyd, Clare M
  • Coyle, Anthony J
  • Humbles, Alison A

publication date

  • April 2011

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