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.
journal_name
Am J Respir Crit Care Medauthors
Kearley J,Erjefalt JS,Andersson C,Benjamin E,Jones CP,Robichaud A,Pegorier S,Brewah Y,Burwell TJ,Bjermer L,Kiener PA,Kolbeck R,Lloyd CM,Coyle AJ,Humbles AAdoi
10.1164/rccm.200909-1462OCsubject
Has Abstractpub_date
2011-04-01 00:00:00pages
865-75issue
7eissn
1073-449Xissn
1535-4970pii
200909-1462OCjournal_volume
183pub_type
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journal_title:American journal of respiratory and critical care medicine
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