First Author | van de Wetering D | Year | 2009 |
Journal | Int Immunol | Volume | 21 |
Issue | 2 | Pages | 145-53 |
PubMed ID | 19088061 | Mgi Jnum | J:319975 |
Mgi Id | MGI:6867140 | Doi | 10.1093/intimm/dxn132 |
Citation | van de Wetering D, et al. (2009) IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T cell function differentially from IL-12. Int Immunol 21(2):145-53 |
abstractText | NK and NK-like T cells play an essential role in linking innate and adaptive immunity through their ability to secrete IFN-gamma. The exact trigger initiating production of IFN-gamma is uncertain. Antigen-presenting cell (APC)-derived IL-12 is thought to be the classical IFN-gamma-inducing cytokine but requires an additional stimulus such as IFN-gamma 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-gamma production in NK and NK-like T cells. Herein, we characterized the effect of IL-23 on IFN-gamma secretion by NK and NK-like T cells. Our findings show that IL-23 and IL-18 synergistically elicit IFN-gamma production in NK-like T cells but not in NK cells. In contrast, IL-12 together with IL-18-induced secretion of IFN-gamma 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-18Ralpha. 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 T(h)1 differentiation, via induction of IFN-gamma, which provides the additional stimulus needed for APC to subsequently produce IL-12. |