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.
journal_name
Int Immunoljournal_title
International immunologyauthors
Finotto S,Hausding M,Doganci A,Maxeiner JH,Lehr HA,Luft C,Galle PR,Glimcher LHdoi
10.1093/intimm/dxh281subject
Has Abstractpub_date
2005-08-01 00:00:00pages
993-1007issue
8eissn
0953-8178issn
1460-2377pii
dxh281journal_volume
17pub_type
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