IL-23 modulates CD56+/CD3- NK Cell and CD56+/CD3+ NK-like T Cell function differentially from IL-12

NK and NK-like T cells play an essential role in linking innate and adaptive immunity through their ability to secrete IFN-γ. The exact trigger initiating production of IFN-γ is uncertain. Antigen-presenting cell (APC)-derived IL-12 is thought to be the classical IFN-γ-inducing cytokine but requires an additional stimulus such as IFN-γ itself. IL-23 and IL-18 are among the first cytokines secreted by APC in response to binding of pathogen-associated molecular patterns such as LPS. Thus, early APC-derived IL-23 may be an initial trigger of IFN-γ production in NK and NK-like T cells. Herein, we characterized the effect of IL-23 on IFN-γ secretion by NK and NK-like T cells. Our findings show that IL-23 and IL-18 synergistically elicit IFN-γ production in NK-like T cells but not in NK cells. In contrast, IL-12 together with IL-18-induced secretion of IFN-γ in both populations. The observed synergy between IL-23 and IL-18 in NK-like T cells coincided with IL-23-mediated up-regulation of IL-18Rα. Furthermore, IL-23 up-regulated CD56 expression in NK-like T cells and, together with IL-18, induced proliferation of NK and NK-like T cells. We postulate a role for APC-derived IL-23 in the activation of NK and NK-like T cells early in infection and in shaping Th1 differentiation, via induction of IFN-γ, which provides the additional stimulus needed for APC to subsequently produce IL-12.