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
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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-κB 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.
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- Authors
- Rehli, M., Sulzbacher, S., Pape, S., Ravasi, T., Wells, C. A., Heinz, S., Söllner, L., El Chartouni, C., Krause, S. W., Steingrimsson, E., Hume, D. A., & Andreesen, R.
- Affiliations
- University of Regensburg (DE)
- The University of Queensland (AU)
- Department of Hematology and Oncology, University of Regensburg , Regensburg ,
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland , Reykjavik ,
- Corresponding author
- Rehli, Michael
- Sulzbacher, Sabine
- Pape, Sabine
- Heinz, Sven
- Andreesen, Reinhard
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06-01
- Volume
- 174
- Issue
- 11
- Pages
- 7111-7122
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2145711185
- Cited by
- 75
- References
- 36
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 3 · 2012: 8
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Griffith Research Online (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft
- University of California, San Diego
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- TFEC, macrophages, IL-4, IL-13, STAT6, granulocyte colony-stimulating factor receptor, CSF3R, alternative activation, Th2 cytokines, LPS, NF-κB, myeloid cells, gene expression, transcriptome
- MeSH terms
- Animals, Base Sequence, Bone Marrow Cells, Cell Line, Cells, Cultured, Lipopolysaccharides, Macrophages, Mice, Inbred BALB C, Molecular Sequence Data, Transcription Factors, Signal Transduction, Trans-Activators, Interleukin-4, Up-Regulation, Immunophenotyping, Receptors, Granulocyte Colony-Stimulating Factor, Helix-Loop-Helix Motifs, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, STAT6 Transcription Factor, Mice, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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