A stage-specific functional role of the leucine zipper transcription factor c-Maf in lung Th2 cell differentiation

Eur J Immunol. 2004 Dec;34(12):3401-12. doi: 10.1002/eji.200425121.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • DNA-Binding Proteins
  • Interleukin-5
  • Maf protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-maf
  • Transcription Factors
  • Interleukin-4