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


OBJECTIVE
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.


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.
Department of Respiratory, Inflammation, and Autoimmunity, MedImmune LLC, Gaithersburg, MD 20878, USA.
Jennifer
J
Kearley
Jonas S
JS
Erjefalt
Cecilia
C
Andersson
Ebony
E
Benjamin
Carla P
CP
Jones
Annette
A
Robichaud
Sophie
S
Pegorier
Yambasu
Y
Brewah
Timothy J
TJ
Burwell
Leif
L
Bjermer
Peter A
PA
Kiener
Roland
R
Kolbeck
Clare M
CM
Lloyd
Anthony J
AJ
Coyle
Alison A
AA
Humbles
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016906:Interleukin-9 / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric
D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D016906:Interleukin-9; D012333:RNA, Messenger; D010047:Ovalbumin