Asthmatic changes in mice lacking T-bet are mediated by IL-13

Details

Serval ID
serval:BIB_B81B91DC27A4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Asthmatic changes in mice lacking T-bet are mediated by IL-13
Journal
International Immunology
Author(s)
Finotto  S., Hausding  M., Doganci  A., Maxeiner  J. H., Lehr  H. A., Luft  C., Galle  P. R., Glimcher  L. H.
ISSN
0953-8178 (Print)
Publication state
Published
Issued date
2005
Volume
17
Number
8
Pages
993-1007
Notes
PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S
Abstract
Mice with a targeted deletion of the T-bet gene exhibit spontaneous airway hyperresponsiveness (AHR), airway inflammation, enhanced recovery of T(h)2 cytokines from bronchoalveolar lavage fluid, sub-epithelial collagen deposition and myofibroblast transformation. Here we analyze the mechanisms responsible for the chronic airway remodeling observed in these mice. CD4+ T cells isolated from the lung of T-bet-deficient mice were spontaneously activated CD44(high)CD69(high) memory T cells, with a typical T(h)2 cytokine profile. Neutralization of IL-13 but not IL-4 resulted in amelioration of AHR in airways of mice lacking T-bet. IL-13 blockade also led to reduced eosinophilia and decreased vimentin, transforming growth factor beta (TGF-beta) and alpha smooth muscle actin (alphaSMA) levels. T-bet(-/-) lung fibroblasts proliferated very rapidly and released increased amounts of TGF-beta. Interestingly, neutralization of TGF-beta ameliorated aspects of the chronic airway remodeling phenotype but did not reduce AHR. These data highlight a T-bet-directed function for IL-13 in controlling lung remodeling that is both dependent on and independent of its interaction with TGF-beta in the asthmatic airway
Keywords
Actins/metabolism/Animals/Asthma/etiology/genetics/immunology/Pathology/CD4-Positive T-Lymphocytes/Cells,Cultured/Cytokines/biosynthesis/DNA-Binding Proteins/Fibroblasts/Immunologic Memory/Interleukin-13/antagonists & inhibitors/Interleukin-4/Lung/Lymphocyte Activation/Mice/Mice,Inbred C57BL/Mice,Knockout/Smad3 Protein/Smad7 Protein/T-Box Domain Proteins/Trans-Activators/Transcription Factors/deficiency/Transforming Growth Factor beta/Vimentin
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 18:34
Last modification date
20/08/2019 15:26
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