NK–DC interaction for elicitation of an innate IFN-γ–IL-27 axis. Innate stimuli from the site of immunization (in this case, CFA) stimulate DC in the draining LN to produce IL-12 and IL-18, which act on the resident NK cells. In response, the NK cells produce IFN-γ, which acts on the DC. The DC respond by producing IL-27, which elicits more IFN-γ from the NK cells. IFN-γ triggers production of CXCR3 ligands by DC, which recruit additional CXCR3-expressing NK cells to the LN, to further amplify the positive feedback loop. The resulting IL-27 causes suppression of the Th17 response through direct and indirect effects, and the IFN-γ attenuates the Th1 and Th17 adaptive immunity by causing death of effector T cells. The positive feedback loop is ultimately mitigated by IL-10 produced in part by the interacting NK and DC cells themselves.
