Published January 1, 2012
| Version v1
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CD8 Lineage-specific Regulation of Interleukin-7 Receptor Expression by the Transcriptional Repressor Gfi1
Creators
- 1. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA
- 2. Sabanci Univ, FENS, Biol Sci & Bioengn Program, TR-34956 Istanbul, Turkey
- 3. NCI, Sci Applicat Int Corp Frederick, Canc Res & Dev Ctr, Frederick, MD 21702 USA
- 4. Univ Montreal, Dept Microbiol & Immunol, Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada
- 5. Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey
Description
Interleukin-7 receptor alpha (IL-7R alpha) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7R alpha expression with diverse roles in T cell biology. Here we identify the transcriptional repressor, growth factor independent-1 (Gfi1), as a novel intermediary in glucocorticoid-induced IL-7R alpha up-regulation. We found Gfi1 to be a major inhibitory target of dexamethasone by microarray expression profiling of 3B4.15 T-hybridoma cells. Concordantly, retroviral transduction of Gfi1 significantly blunted IL-7R alpha up-regulation by dexamethasone. To further assess the role of Gfi1 in vivo, we generated bacterial artificial chromosome (BAC) transgenic mice, in which a modified Il7r locus expresses GFP to report Il7r gene transcription. By introducing this BAC reporter transgene into either Gfi1-deficient or Gfi1-transgenic mice, we document in vivo that IL-7R alpha transcription is up-regulated in the absence of Gfi1 and down-regulated when Gfi1 is overexpressed. Strikingly, the in vivo regulatory role of Gfi1 was specific for CD8(+), and not CD4(+) T cells or immature thymocytes. These results identify Gfi1 as a specific transcriptional repressor of the Il7r gene in CD8 T lymphocytes in vivo.
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