title: Transcriptional regulation of the IL-7Rα gene by dexamethasone and IL-7 in primary human CD8 T cells.
abstract: Interleukin-7 is essential for the development and maintenance of T cells, and the expression of the IL-7 receptor is tightly regulated at every stage of the T cell's lifespan. In mature CD8 T cells, IL-7 plays important roles in cell survival, peripheral homeostasis, and cytolytic function. The IL-7 receptor alpha-chain (CD127) is expressed at high levels on naïve and memory cells, but it is rapidly downregulated upon IL-7 stimulation. In this study, we illustrate the dynamicity of the CD127 promoter and show that it possesses positive as well as negative regulatory sites involved in upregulating and downregulating CD127 expression, respectively. We cloned the CD127 gene promoter and identified key cis-regulatory elements required for CD127 expression in mature resting primary CD8 T cells. The core promoter necessary for efficient basal transcription is contained within the first 262 bp upstream of the TATA box. Additional positive regulatory elements are located between -1200 and -2406 bp, conferring a further 2- to 4-fold enhancement in gene expression. While transcription of the CD127 gene is increased directly through a glucocorticoid response element located between -2255 and -2269 bp upstream of the TATA box, we identified a suppressive region that lies upstream of 1760 bp from the TATA box, which is likely involved in the IL-7-mediated suppression of CD127 transcription. Finally, we illustrated IL-7 does not bias alternative splicing of CD127 transcripts in primary human CD8 T cells.
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H8L6, Canada.|Departments of Medicine, and Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H8M5, Canada.
authors.forename: Juzer A
authors.initials: JA
authors.lastname: Kakal
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H8L6, Canada.
authors.forename: Feras M
authors.initials: FM
authors.lastname: Ghazawi
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H8L6, Canada.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Faller
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H8L6, Canada.|Departments of Medicine, and Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H8M5, Canada.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Sugden
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H8L6, Canada.
authors.forename: Parmvir
authors.initials: P
authors.lastname: Parmar
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H8L6, Canada. pmacpherson@toh.ca.|Departments of Medicine, and Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H8M5, Canada. pmacpherson@toh.ca.|Division of Infectious Diseases, The Ottawa Hospital, General Campus, Box 223, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada. pmacpherson@toh.ca.
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacPherson
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic
chemical_list: D000893:Anti-Inflammatory Agents; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D003907:Dexamethasone
keywords: CD127; CD127 promoter; Cytotoxic T-lymphocytes; Interleukin-7; Interleukin-7 receptor