title: CD8 lineage-specific regulation of interleukin-7 receptor expression by the transcriptional repressor Gfi1.
abstract: Interleukin-7 receptor α (IL-7Rα) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7Rα 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-7Rα 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-7Rα 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-7Rα 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.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Davinna L
authors.initials: DL
authors.lastname: Ligons
authors.forename: Ceren
authors.initials: C
authors.lastname: Tuncer
authors.forename: Brett A
authors.initials: BA
authors.lastname: Linowes
authors.forename: Izzet Mehmet
authors.initials: IM
authors.lastname: Akcay
authors.forename: Sema
authors.initials: S
authors.lastname: Kurtulus
authors.forename: Emre
authors.initials: E
authors.lastname: Deniz
authors.forename: Belkis
authors.initials: B
authors.lastname: Atasever Arslan
authors.forename: Safak Isil
authors.initials: SI
authors.lastname: Cevik
authors.forename: Hilary R
authors.initials: HR
authors.lastname: Keller
authors.forename: Megan A
authors.initials: MA
authors.lastname: Luckey
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
authors.forename: Tulin
authors.initials: T
authors.lastname: Ersahin
authors.forename: Rengul
authors.initials: R
authors.lastname: Atalay
authors.forename: Batu
authors.initials: B
authors.lastname: Erman
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity / Q000187:drug effects / Q000502:physiology; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D005938:Glucocorticoids; D020395:Receptors, Interleukin-7; D012097:Repressor Proteins; D014157:Transcription Factors; C415350:interleukin-7 receptor, alpha chain; D003907:Dexamethasone