title: 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.
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.
authors: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma, Rome, Italy.
authors: Graziella
authors: G
authors: Curtale
authors: Franca
authors: F
authors: Citarella
authors: Claudia
authors: C
authors: Carissimi
authors: Marina
authors: M
authors: Goldoni
authors: Nicoletta
authors: N
authors: Carucci
authors: Valerio
authors: V
authors: Fulci
authors: Debora
authors: D
authors: Franceschini
authors: Francesca
authors: F
authors: Meloni
authors: Vincenzo
authors: V
authors: Barnaba
authors: Giuseppe
authors: G
authors: Macino
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D053200:Fas-Associated Death Domain Protein / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000276:immunology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology*; D035683:MicroRNAs / Q000276:immunology / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D020218:Response Elements / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; C508594:IL2 protein, human; D007376:Interleukin-2; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D050783:Proto-Oncogene Proteins c-ets; D011948:Receptors, Antigen, T-Cell; D018808:Transcription Factor AP-1