6533b7d8fe1ef96bd126afdb

RESEARCH PRODUCT

TGF-beta regulates airway responses via T cells.

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Abstract Allergic asthma is characterized by airway hyperreactivity, inflammation, and a Th2-type cytokine profile favoring IgE production. Beneficial effects of TGF-β and conflicting results regarding the role of Th1 cytokines have been reported from murine asthma models. In this study, we examined the T cell as a target cell of TGF-β-mediated immune regulation in a mouse model of asthma. We demonstrate that impairment of TGF-β signaling in T cells of transgenic mice expressing a dominant-negative TGF-β type II receptor leads to a decrease in airway reactivity in a non-Ag-dependent model. Increased serum levels of IFN-γ can be detected in these animals. In contrast, after injection of OVA adsorbed to alum and challenge with OVA aerosol, transgenic animals show an increased airway reactivity and inflammation compared with those of wild-type animals. IL-13 levels in bronchoalveolar lavage fluid and serum as well as the number of inducible NO synthase-expressing cells in lung infiltrates were increased in transgenic animals. These results demonstrate an important role for TGF-β signaling in T cells in the regulation of airway responses and suggest that the beneficial effects observed for TGF-β in airway hyperreactivity and inflammation may be due to its regulatory effects on T cells.