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

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Author

  • 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
Show all

Summary, in English

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.

Publishing year

2011

Language

English

Pages

865-875

Publication/Series

American Journal of Respiratory and Critical Care Medicine

Volume

183

Issue

7

Document type

Journal article

Publisher

American Thoracic Society

Topic

  • Respiratory Medicine and Allergy

Keywords

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

Status

Published

Research group

  • Airway Inflammation and Immunology

ISBN/ISSN/Other

  • ISSN: 1535-4970