Transcription factor Tfec contributes to the IL-4-inducible expression of a small group of genes in mouse macrophages including the granulocyte colony-stimulating factor receptor

Michael Rehli, Sabine Sulzbacher, Sabine Pape, Timothy Ravasi, Christine A Wells, Sven Heinz, Liane Söllner, Carol El Chartouni, Stefan W Krause, Eirikur Steingrimsson, David A Hume, Reinhard Andreesen

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Expression of the mouse transcription factor EC (Tfec) is restricted to the myeloid compartment, suggesting a function for Tfec in the development or function of these cells. However, mice lacking Tfec develop normally, indicating a redundant role for Tfec in myeloid cell development. We now report that Tfec is specifically induced in bone marrow-derived macrophages upon stimulation with the Th2 cytokines, IL-4 and IL-13, or LPS. LPS induced a rapid and transient up-regulation of Tfec mRNA expression and promoter activity, which was dependent on a functional NF-kappaB site. IL-4, however, induced a rapid, but long-lasting, increase in Tfec mRNA, which, in contrast to LPS stimulation, also resulted in detectable levels of Tfec protein. IL-4-induced transcription of Tfec was absent in macrophages lacking Stat6, and its promoter depended on two functional Stat6-binding sites. A global comparison of IL-4-induced genes in both wild-type and Tfec mutant macrophages revealed a surprisingly mild phenotype with only a few genes affected by Tfec deficiency. These included the G-CSFR (Csf3r) gene that was strongly up-regulated by IL-4 in wild-type macrophages and, to a lesser extent, in Tfec mutant macrophages. Our study also provides a general definition of the transcriptome in alternatively activated mouse macrophages and identifies a large number of novel genes characterizing this cell type.
Original languageEnglish
Pages (from-to)7111-22
Number of pages12
JournalThe Journal of Immunology
Volume174
Issue number11
Publication statusPublished - 1 Jun 2005

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Bone Marrow Cells
  • Cell Line
  • Cells, Cultured
  • Gene Expression Profiling
  • Helix-Loop-Helix Motifs
  • Immunophenotyping
  • Interleukin-4
  • Lipopolysaccharides
  • Macrophages
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Granulocyte Colony-Stimulating Factor
  • STAT6 Transcription Factor
  • Signal Transduction
  • Trans-Activators
  • Transcription Factors
  • Up-Regulation

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