Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Graziella Curtale1,
  2. Franca Citarella1,
  3. Claudia Carissimi1,
  4. Marina Goldoni1,
  5. Nicoletta Carucci1,
  6. Valerio Fulci1,
  7. Debora Franceschini2,
  8. Francesca Meloni2,
  9. Vincenzo Barnaba2, and
  10. Giuseppe Macino1
  1. 1Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma; and
  2. 2Dipartimento di Medicina Interna, Sapienza Università di Roma, Rome, Italy


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.

  • Submitted June 5, 2009.
  • Accepted October 14, 2009.
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