IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells.
Constitutive expression of IL9 in the lungs of transgenic (Tg) mice resulted in an asthma-like phenotype consisting of lymphocytic and eosinophilic lung inflammation, mucus hypersecretion and mast cell hyperplasia. Several T(h)2 cytokines including IL4, IL5 and IL13 were expressed in the lung in response to Tg IL9. IL13 was absolutely necessary for the development of lung pathology. To understand how IL9 induces IL13-dependent lung inflammation and mucus production, we sought the IL13-producing cells. Surprisingly, we found that the absence of T cells and B cells in recombinase-activating gene 1 (RAG1)-deficient IL9 Tg mice enhanced lung inflammation and dramatically enhanced IL13 production. In addition, the lack of mast cells or eosinophils in IL9 Tg mice did not affect IL13 levels in the lung. In situ hybridization for IL13 on lung sections from RAG1-/- IL9 Tg mice revealed that airway epithelial cells were the major IL13-producing cell type. Our results implicate the lung epithelium as a potentially important source of inflammatory cytokines in asthma.
Temann
Ulla-Angela
UA
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Laouar
Yasmina
Y
Eynon
Elizabeth E
EE
Homer
Robert
R
Flavell
Richard A
RA
D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D016654:Genes, RAG-1 / Q000235:genetics / Q000502:physiology; D018793:Interleukin-13 / Q000378:metabolism*; D015848:Interleukin-5 / Q000502:physiology; D016906:Interleukin-9 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D050800:STAT6 Transcription Factor / Q000378:metabolism
D018793:Interleukin-13; D015848:Interleukin-5; D016906:Interleukin-9; D050800:STAT6 Transcription Factor