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.

An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and AICD in T lymphocytes / Curtale, G; Citarella, Franca; Carissimi, Claudia; Goldoni, M; Carucci, N; Fulci, Valerio; Franceschini, D; Meloni, F; Barnaba, Vincenzo; Macino, Giuseppe. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 115 (2):(2010), pp. 265-273. [10.1182/blood-2009-06-225987]

An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and AICD in T lymphocytes

CITARELLA, Franca;CARISSIMI, Claudia;FULCI, Valerio;BARNABA, Vincenzo;MACINO, Giuseppe
2010

Abstract

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.
2010
01 Pubblicazione su rivista::01a Articolo in rivista
An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and AICD in T lymphocytes / Curtale, G; Citarella, Franca; Carissimi, Claudia; Goldoni, M; Carucci, N; Fulci, Valerio; Franceschini, D; Meloni, F; Barnaba, Vincenzo; Macino, Giuseppe. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 115 (2):(2010), pp. 265-273. [10.1182/blood-2009-06-225987]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/363063
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 116
  • Scopus 261
  • ???jsp.display-item.citation.isi??? 234
social impact