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

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

Research output: Contribution to journalArticlepeer-review


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-beta 1, 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.
Original languageEnglish
Pages (from-to)865-875
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number7
Publication statusPublished - 2011

Subject classification (UKÄ)

  • Respiratory Medicine and Allergy

Free keywords

  • IL-9
  • mast cells
  • asthma
  • airway remodeling
  • AHR


Dive into the research topics of 'IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways'. Together they form a unique fingerprint.

Cite this