| An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes. | |
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MedLine Citation:
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PMID: 19965651 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation of the T cell-mediated immune response has been associated with changes in the expression of specific microRNAs (miRNAs). However, the role of miRNAs in the development of an effective immune response is just beginning to be explored. This study focuses on the functional role of miR-146a in T lymphocyte-mediated immune response and provides interesting clues on the transcriptional regulation of miR-146a during T-cell activation. We show that miR-146a is low in human naive T cells and is abundantly expressed in human memory T cells; consistently, miR-146a is induced in human primary T lymphocytes upon T-cell receptor (TCR) stimulation. Moreover, we identified NF-kB and c-ETS binding sites as required for the induction of miR-146a transcription upon TCR engagement. Our results demonstrate that several signaling pathways, other than inflammation, are influenced by miR-146a. In particular, we provide experimental evidence that miR-146a modulates activation-induced cell death (AICD), acting as an antiapoptotic factor, and that Fas-associated death domain (FADD) is a target of miR-146a. Furthermore, miR-146a enforced expression impairs both activator protein 1 (AP-1) activity and interleukin-2 (IL-2) production induced by TCR engagement, thus suggesting a role of this miRNA in the modulation of adaptive immunity. |
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Authors:
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Graziella Curtale; Franca Citarella; Claudia Carissimi; Marina Goldoni; Nicoletta Carucci; Valerio Fulci; Debora Franceschini; Francesca Meloni; Vincenzo Barnaba; Giuseppe Macino |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-12 |
Journal Detail:
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Title: Blood Volume: 115 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-15 Completed Date: 2010-01-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 265-73 Citation Subset: AIM; IM |
Affiliation:
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Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma, Rome, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptive Immunity
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physiology* Cell Death / physiology Fas-Associated Death Domain Protein / immunology, metabolism Gene Expression Regulation / physiology* Humans Interleukin-2 / biosynthesis*, immunology Jurkat Cells Lymphocyte Activation / physiology* MicroRNAs / immunology, metabolism* Proto-Oncogene Proteins c-ets / immunology, metabolism Receptors, Antigen, T-Cell / immunology, metabolism Response Elements / physiology Signal Transduction / physiology T-Lymphocytes / cytology, immunology, metabolism* Transcription Factor AP-1 / immunology, metabolism Transcription, Genetic / physiology |
| Chemical | |
Reg. No./Substance:
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0/FADD protein, human; 0/Fas-Associated Death Domain Protein; 0/IL2 protein, human; 0/Interleukin-2; 0/MIRN146 microRNA, human; 0/MicroRNAs; 0/Proto-Oncogene Proteins c-ets; 0/Receptors, Antigen, T-Cell; 0/Transcription Factor AP-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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