Format

Send to

Choose Destination
Am J Respir Crit Care Med. 2011 Apr 1;183(7):865-75. doi: 10.1164/rccm.200909-1462OC. Epub 2010 Oct 22.

IL-9 governs allergen-induced mast cell numbers in the lung and chronic remodeling of the airways.

Author information

1
Department of Respiratory, Inflammation, and Autoimmunity, MedImmune LLC, Gaithersburg, MD 20878, USA.

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.

PMID:
20971830
PMCID:
PMC3385369
DOI:
10.1164/rccm.200909-1462OC
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center