Schematic representation modeling the induction of miR-155 after NK cell activation and its role in regulating IFN-γ production. miR-155 expression was induced after activation of resting NK cells via IL18 alone, via CD16 activation alone, but not via IL-12 alone; however, the combination of IL-12 with either IL-18 or CD16 activation induced miR-155 in a synergistic fashion. This synergism was dependent on the induction of the IL-18R by IL-12, whereas the synergistic induction of miR-155 noted with CD16 and IL-12 possibly results from enhanced intracellular signaling downstream of CD16 (dashed arrow). miR-155 targets the 5′ inositol phosphatase SHIP1, thereby down-modulating SHIP1 expression, which in turn promotes the prolonged activation of the PI3K pathway and subsequent enhanced production of IFN-γ.