Extended Data Fig. 3: IL-12/18 antagonizes IFN-α signaling.

RNA-seq or flow cytometry was performed on sorted NK cells (CD3ε⁻ TCRβ⁻ CD19⁻ F4/80⁻ NK1.1⁺) cultured for 3 h with indicated cytokine conditions. n = 3. a, Bar plots show mean of normalized counts of Stat1 transcript across various cytokine conditions assayed by RNA-seq. b, Graphs depict percent of NK cells positive for intracellular IFN-γ staining (left), mean fluorescence intensity (MFI) of IFN-γ⁺ cells (middle), and MFI of p-STAT4 (Tyr; right). Bar indicates mean ± SD. P-values are calculated by unpaired two-sided Student’s t-test comparing WT to Stat1^–/–. c, Bar plot depicts number of antagonistic IL-12/18:IFN-α genes, as shown in Extended Data Fig. 2d. d, Left panel shows heatmap of row-scaled log-transformed expression values of the 86 common differentially expressed genes between IFN-α, IL-12/IL-18 and IL-2/IL-15, hierarchically clustered into 4 groups. Box plots of z-scores from each cluster are depicted in the right panel. Centre, median; box limits, first and third percentiles; whiskers, 1.5 × interquartile range. Dotted lines show median z-score of IFN-α plus IL-12/IL-18 plus IL-2/15 condition. Tiles to the left of gene names indicate whether the genes are bound by STAT1 (green), STAT4 (blue), or STAT5 (orange) by ChIP-seq.