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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

Curtale, Graziella, Citarella, Franca, Carissimi, Claudia, Goldoni, Marina, Carucci, Nicoletta, Fulci, Valerio, Franceschini, Debora, Meloni, Francesca, Barnaba, Vincenzo, Macino, Giuseppe·2010·Blood
DOI 10.1182/blood-2009-06-225987
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Abstract

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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  • miR-146a expression is inducible on activation in T cells, dendritic cells, and macrophages.

    “Mir-146a expression has been shown to be inducible on activation in a set of mature hematopoietic cells, namely in T cells, 50 dendritic cells, 38 and macrophages.16”

    From Macrophage development from HSCs requires PU.1-coordinated microRNA expression (2011) · cites this paper as [50]

Citations

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Metadata

Authors
Curtale, G., Citarella, F., Carissimi, C., Goldoni, M., Carucci, N., Fulci, V., Franceschini, D., Meloni, F., Barnaba, V., & Macino, G.
Affiliations
  • Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma; and
  • Dipartimento di Medicina Interna, Sapienza Università di Roma, Rome, Italy
Venue
Blood
Publisher
American Society of Hematology
Published
2010-01-14
Volume
115
Issue
2
Pages
265-273
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2009-06-225987
Cited by
263
References
5
Language
en

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