Asthmatic changes in mice lacking T-bet are mediated by IL-13
| Autor: | Peter R. Galle, Laurie H. Glimcher, Cornelia Luft, Aysefa Doganci, Hans A. Lehr, Susetta Finotto, Joachim Maxeiner, Michael Hausding |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunology chemical and pharmacologic phenomena Vimentin Lymphocyte Activation Smad7 Protein Mice Transforming Growth Factor beta medicine Animals Immunology and Allergy Eosinophilia Smad3 Protein Lung Cells Cultured Mice Knockout Interleukin-13 biology medicine.diagnostic_test Chemistry CD69 hemic and immune systems General Medicine Transforming growth factor beta Fibroblasts respiratory system Actins Asthma respiratory tract diseases DNA-Binding Proteins Mice Inbred C57BL Bronchoalveolar lavage medicine.anatomical_structure Interleukin 13 Trans-Activators biology.protein Cytokines Interleukin-4 medicine.symptom T-Box Domain Proteins Immunologic Memory Myofibroblast Transcription Factors |
| Zdroj: | International Immunology. 17:993-1007 |
| ISSN: | 1460-2377 0953-8178 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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