CD8 Lineage-specific Regulation of Interleukin-7 Receptor Expression by the Transcriptional Repressor Gfi1

Ligons D. L. , Tuncer C., Linowes B. A. , Akcay I. M. , Kurtulus S., Deniz E., ...More

JOURNAL OF BIOLOGICAL CHEMISTRY, vol.287, no.41, pp.34386-34399, 2012 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 287 Issue: 41
  • Publication Date: 2012
  • Doi Number: 10.1074/jbc.m112.378687
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.34386-34399
  • Istanbul Technical University Affiliated: Yes


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.