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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lipsky, Peter E. Thümmler, Katja Prots, Iryna Schulze-Koops, Hendrik Zhou, Qihui Skapenko, Alla Kremmer, Elisabeth Haupt, Sonja |
| Description | Country affiliation: Germany Author Affiliation: Zhou Q ( Division of Rheumatology, Department of Internal Medicine IV, University of Munich, 80336 Munich, Germany.) |
| Abstract | Because of the numerous targets of microRNAs (miRNAs), functional dissection of specific miRNA/mRNA interactions is important to understand the complex miRNA regulatory mechanisms. Glycoprotein A repetitions predominant (GARP) is specifically expressed on regulatory CD25(+) CD4 T cells upon their activation. GARP has a long 3' untranslated region containing five highly conserved regions suggesting miRNA regulation of its expression. Although GARP is physiologically expressed on a cell subset characterized by stringent control of proliferation, amplification of the GARP gene has been found in many tumors characterized by uncontrolled proliferation. In this study, we investigated in detail miRNA regulation of GARP expression, in particular by miR-142-3p, and dissected the functional outcome of miR-142-3p/GARP mRNA interaction. We demonstrate that miR-142-3p binds directly to the 3' untranslated region of GARP and represses GARP protein expression by Argonaute 2-associated degradation of GARP mRNA. Functionally, miR-142-3p-mediated regulation of GARP is involved in the expansion of CD25(+) CD4 T cells in response to stimulation. The data indicate that miR-142-3p regulates GARP expression on CD25(+) CD4 T cells and, as a result, their expansion in response to activation. Our data provide novel insight into the molecular mechanisms controlling regulatory T cell expansion. They may also have implications for understanding tumor cell biology. |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| Journal | The Journal of Immunology |
| Issue Number | 12 |
| Volume Number | 190 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2013-06-15 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cd4-positive T-lymphocytes Immunology Gene Expression Regulation Lymphocyte Activation Genetics Membrane Proteins Biosynthesis Micrornas 3' Untranslated Regions Animals Blotting, Western Cell Proliferation Fluorescent Antibody Technique Hek293 Cells Interleukin-2 Receptor Alpha Subunit Metabolism Jurkat Cells Molecular Sequence Data Real-time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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