title: IL-7 downregulates IL-7Rα expression in human CD8 T cells by two independent mechanisms.
abstract: Interleukin (IL)-7 is an essential nonredundant cytokine, and throughout the lifespan of a T-cell signaling via the IL-7 receptor influences cell survival, proliferation and differentiation. It is therefore no surprise that expression of the IL-7 receptor alpha-chain (CD127) is tightly regulated. We have previously shown that IL-7 downregulates expression of CD127 at the cell surface and now elucidate the kinetics of that suppression and demonstrate that IL-7 downregulates CD127 transcripts and surface protein in primary human CD8 T cells by two separate pathways. We show that IL-7 induces the initial reduction in cell-surface CD127 protein independent of transcriptional suppression, which is delayed by 40-60 min. Although IL-7-mediated downregulation of CD127 transcripts is dependent on Janus kinase (JAK)/STAT5, the early downregulation of surface CD127 protein is independent of JAK activity. The data further illustrate that low levels of IL-7 induce smaller and transient decreases in CD127 transcripts and surface protein, whereas higher concentrations induce more profound and sustained suppression. Such flexibility in receptor expression likely allows for fine-tuned immune responses in human CD8 T cells in different microenvironments and in response to different immunological challenges.
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Feras M
authors.initials: FM
authors.lastname: Ghazawi
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Faller
authors.forename: Scott M
authors.initials: SM
authors.lastname: Sugden
authors.forename: Juzer A
authors.initials: JA
authors.lastname: Kakal
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacPherson
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D053612:Janus Kinases / Q000378:metabolism; D019169:Jurkat Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D015851:Interleukin-7; D012333:RNA, Messenger; D020395:Receptors, Interleukin-7; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C415350:interleukin-7 receptor, alpha chain; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases