| IL-7 downregulates IL-7Rα expression in human CD8 T cells by two independent mechanisms. | |
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MedLine Citation:
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PMID: 23207282 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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.Immunology and Cell Biology advance online publication, 4 December 2012; doi:10.1038/icb.2012.69. |
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Authors:
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Feras M Ghazawi; Elliott M Faller; Scott M Sugden; Juzer A Kakal; Paul A Macpherson |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-04 |
Journal Detail:
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Title: Immunology and cell biology Volume: - ISSN: 1440-1711 ISO Abbreviation: Immunol. Cell Biol. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8706300 Medline TA: Immunol Cell Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Ottawa Hospital Research Institute, Ottawa, Ontario, Canada [2] Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. |
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