| First Author | Finotto S | Year | 2005 |
| Journal | Int Immunol | Volume | 17 |
| Issue | 8 | Pages | 993-1007 |
| PubMed ID | 16000330 | Mgi Jnum | J:99969 |
| Mgi Id | MGI:3584310 | Doi | 10.1093/intimm/dxh281 |
| Citation | Finotto S, et al. (2005) Asthmatic changes in mice lacking T-bet are mediated by IL-13. Int Immunol 17(8):993-1007 |
| abstractText | 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. |
