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IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways.
Kearley, Jennifer 1; Erjefalt, Jonas S. 2; Andersson, Cecilia 2; Benjamin, Ebony 1; Jones, Carla P. 3; Robichaud, Annette 4; Pegorier, Sophie 3; Brewah, Yambasu 1; Burwell, Timothy J. 1; Bjermer, Leif 2; Kiener, Peter A. 1; Kolbeck, Roland 1; Lloyd, Clare M. 3; Coyle, Anthony J. 1; Humbles, Alison A. 1
[Article] American Journal of Respiratory & Critical Care Medicine. 183(7):865-875, April 1, 2011.

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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.