| First Author | Trotta R | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 15 | Pages | 3478-85 |
| PubMed ID | 22378844 | Mgi Jnum | J:183765 |
| Mgi Id | MGI:5319245 | Doi | 10.1182/blood-2011-12-398099 |
| Citation | Trotta R, et al. (2012) miR-155 regulates IFN-gamma production in natural killer cells. Blood 119(15):3478-85 |
| abstractText | MicroRNAs (miRs) are small, noncoding RNA molecules with important regulatory functions whose role in regulating natural killer (NK) cell biology is not well defined. Here, we show that miR-155 is synergistically induced in primary human NK cells after costimulation with IL-12 and IL-18, or with IL-12 and CD16 clustering. Over-expression of miR-155 enhanced induction of IFN-gamma by IL-12 and IL-18 or CD16 stimulation, whereas knockdown of miR-155 or its disruption suppressed IFN-gamma induction in monokine and/or CD16-stimulated NK cells. These effects on the regulation of NK cell IFN-gamma expression were found to be mediated at least in part via miR-155's direct effects on the inositol phosphatase SHIP1. Consistent with this, we observed that modulation of miR-155 overrides IL-12 and IL-18-mediated regulation of SHIP1 expression in NK cells. Collectively, our data indicate that miR-155 expression is regulated by stimuli that strongly induce IFN-gamma in NK cells such as IL-12, IL-18, and CD16 activation, and that miR-155 functions as a positive regulator of IFN-gamma production in human NK cells, at least in part via down-regulating SHIP1. These findings may have clinical relevance for targeting miR-155 in neoplastic disease. |
