Premium
A stage‐specific functional role of the leucine zipper transcription factor c‐Maf in lung Th2 cell differentiation
Author(s) -
Hausding Michael,
Ho ICheng,
Lehr Hans A.,
Weigmann B.,
Lux Christine,
Schipp Mechtild,
Galle Peter R.,
Finotto Susetta
Publication year - 2004
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200425121
Subject(s) - biology , immunology , transcription factor , lung , microbiology and biotechnology , interleukin 13 , interleukin 4 , cytokine , gene , medicine , genetics
Abstract 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.