The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice
J. Clin. Invest. Beichu Guo, et al. 118:1680 doi:10.1172/JCI33342 [Go to this article.]

Figure 6
Type I IFN–mediated IL-27 production in macrophages contributes to inhibition of IL-17 production. (A) CM from IFN-β–treated macrophages suppresses Th17 development. WT, TRIF-deficient, and IFNAR-deficient BMMs were stimulated with IFN-β for 24 hours. Supernatants from IFN-β–stimulated macrophages were used as CM; they were added to Th17 culture and incubated for 72 hours. IL-17 production by CD4⁺ T cells was determined by ELISA. (B) WT and IFNAR-deficient BMMs were stimulated with IFN-β for 24 hours. The level of IL-27 protein was measured by ELISA. Data shown are representative of at least 3 experiments. (C) IFN-β–mediated inhibitory effects on Th17 development are reversed in the presence of anti–IL-27 antibody. CM from IFN-β–stimulated WT macrophages together with anti–IL-27 antibody or control IgG was added to Th17 cell culture. After 72 hours, IL-17 production by CD4⁺ T cells was determined by ELISA. (D) IL-27 contributes to IFN-β–mediated inhibition of encephalitogenic T cells. Lymphocytes isolated from immunized WT mice were restimulated with MOG peptide for 72 hours in the presence of CM from IFN-treated macrophages plus anti–IL-27 antibody or control IgG. IL-17 levels were measured by ELISA. (E) Lymphocytes isolated from immunized IFNAR^–/– mice were restimulated with MOG peptide in the presence of CM from IFN-treated macrophages plus anti–IL-27 antibody. IL-27 treatment was included as a positive control. IL-17 level was measured after 72 hours of culture.