Article: article from journal or magazin.
A stage-specific functional role of the leucine zipper transcription factor c-Maf in lung Th2 cell differentiation.
European Journal of Immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
The transcription factor c-Maf controls IL-4 gene expression in CD4(+) T cells, and its expression is up-regulated in human asthmatic airways after allergen challenge. In the present study, we addressed the role of c-Maf in asthma by studying transgenic (Tg) mice overexpressing c-Maf in CD4(+) T cells under the control of the CD2 promoter. As shown, lung CD4(+) T cells of c-maf-Tg mice produced more IL-5 at the early stage (day 2) of culture in the presence of IL-4 than wild-type control cells. Consistently, c-maf-Tg mice spontaneously showed increased IL-5 expression and eosinophils in the bronchial alveolar lavage fluid (BALF) and activated IL-5 signal transduction via Raf-1 and Ras in lung eosinophils. Finally, IL-13 was suppressed in the BALF of c-maf-Tg mice and in supernatants of Tg lung CD4(+) T cells cultured in the presence of IL-2. Consistently, retroviral overexpression of c-Maf suppressed IL-13 production in developing lung Th2 cells. In summary, c-Maf induces IL-5 production in lung CD4(+) T cells at an early stage, but along with IL-2 suppresses IL-13 production in differentiating lung Th2 cells, thereby explaining the finding that overexpression of c-Maf does not cause airway hyperresponsiveness, a hallmark feature of asthma.
Animals, Cell Differentiation/physiology, Cell Division/physiology, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Eosinophils/metabolism, Interleukin-4/metabolism, Interleukin-5/metabolism, Leucine Zippers/physiology, Lung/metabolism, Mice, Mice, Transgenic, Proto-Oncogene Proteins/genetics, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins c-maf, Th2 Cells/cytology, Th2 Cells/metabolism, Transcription Factors/metabolism
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