Expression of interleukin 9 in the lungs of transgenic mice causes airway inflammation, mast cell hyperplasia, and bronchial hyperresponsiveness.
Interleukin (IL)-9, a pleiotropic cytokine produced by the Th2 subset of T lymphocytes has been proposed as product of a candidate gene responsible for asthma. Its wide range of biological functions on many cell types involved in the allergic immune response suggests a potentially important role in the complex pathogenesis of asthma. To investigate the contributions of IL-9 to airway inflammation and airway hyperresponsiveness in vivo, we created transgenic mice in which expression of the murine IL-9 cDNA was regulated by the rat Clara cell 10 protein promoter. Lung selective expression of IL-9 caused massive airway inflammation with eosinophils and lymphocytes as predominant infiltrating cell types. A striking finding was the presence of increased numbers of mast cells within the airway epithelium of IL-9-expressing mice. Other impressive pathologic changes in the airways were epithelial cell hypertrophy associated with accumulation of mucus-like material within nonciliated cells and increased subepithelial deposition of collagen. Physiologic evaluation of IL-9-expressing mice demonstrated normal baseline airway resistance and markedly increased airway hyperresponsiveness to inhaled methacholine. These findings strongly support an important role for IL-9 in the pathogenesis of asthma.
Temann
U A
UA
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Geba
G P
GP
Rankin
J A
JA
Flavell
R A
RA
D000818:Animals; D001980:Bronchi / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D004848:Epithelium / Q000648:ultrastructure; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006632:Histamine / Q000378:metabolism; D006965:Hyperplasia; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D007507:Therapeutic Irrigation
D016906:Interleukin-9; D006632:Histamine