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

Kearley, Jennifer; Erjefält, Jonas LU ; Andersson, Cecilia LU ; Benjamin, Ebony; Jones, Carla P.; Robichaud, Annette; Pegorier, Sophie; Brewah, Yambasu; Burwell, Timothy J. and Bjermer, Leif LU , et al. (2011) In American Journal of Respiratory and Critical Care Medicine 183(7). p.865-875
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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
keywords
IL-9, mast cells, asthma, airway remodeling, AHR
in
American Journal of Respiratory and Critical Care Medicine
volume
183
issue
7
pages
865 - 875
publisher
Am Thoracic Soc
external identifiers
  • wos:000289318800012
  • scopus:79953327120
ISSN
1535-4970
DOI
10.1164/rccm.200909-1462OC
language
English
LU publication?
yes
id
16d658a1-4c35-4bdb-85fe-d0c172419952 (old id 1966149)
date added to LUP
2011-06-01 10:52:17
date last changed
2017-08-20 03:02:52
@article{16d658a1-4c35-4bdb-85fe-d0c172419952,
  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-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.},
  author       = {Kearley, Jennifer and Erjefält, Jonas and Andersson, Cecilia and Benjamin, Ebony and Jones, Carla P. and Robichaud, Annette and Pegorier, Sophie and Brewah, Yambasu and Burwell, Timothy J. and Bjermer, Leif and Kiener, Peter A. and Kolbec, Roland and Lloyd, Clare M. and Coyle, Anthony J. and Humbles, Alison A.},
  issn         = {1535-4970},
  keyword      = {IL-9,mast cells,asthma,airway remodeling,AHR},
  language     = {eng},
  number       = {7},
  pages        = {865--875},
  publisher    = {Am Thoracic Soc},
  series       = {American Journal of Respiratory and Critical Care Medicine},
  title        = {IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways},
  url          = {http://dx.doi.org/10.1164/rccm.200909-1462OC},
  volume       = {183},
  year         = {2011},
}