IL-21 enhances dendritic cell ability to induce interferon-gamma production by natural killer T cells

Interleukin (IL)-21 shows pleiotropic effects on the proliferation, differentiation, and effector functions of leukocytes. However, the influence of IL-21 on dendritic cell (DC) activation of natural killer T (NKT) cells has not yet been elucidated. In the present study, we examined the effect of IL-21 on murine myeloid DC ability to induce NKT cell production of interferon-γ (IFN-γ) and IL-4. Pretreatment of DCs with IL-21 and α-galactosylceramide (α-GalCer), an NKT cell-specific ligand, resulted in the enhanced ability of the DCs to induce NKT cell production of IFN-γ but not IL-4 in vitro compared to DCs pretreated with α-GalCer alone. A similar effect of IL-21 was observed when DCs pretreated with IL-21 and α-GalCer in vitro were transferred into naïve mice. Direct administration of IL-21 to the mice also enhanced IFN-γ production after injection of α-GalCer. Thus, IL-21 can modify DC ability to selectively enhance NKT cell production of IFN-γ upon stimulation with α-GalCer.