Fig. 4.

Interferon boosts the transcriptional sexually differential immune response. a Principal component analysis (PCA) of GN, MF, and B cells (circles, triangles, and diamonds, respectively) of females and males (pink and light blue) with and without IFN (filled or open shapes, respectively), based on 1000 autosomal genes with the highest standard deviation. Axes are the first three principal components (PCs). b The distribution of the log₂ fold change values between IFN-stimulated MF and unstimulated MF for the IFN upregulated genes in male and/or female MF. Distribution for female samples is shown in pink and for male in light blue. The t test p value between distributions is 2.7 × 10⁻¹³ with permutation p value <0.001. c Expression heatmap of 313 MF IFN-stimulated genes (MF-ISGs) expressed in unstimulated and IFN-stimulated male and female macrophage samples (dataset B). Expression values are trimmed to range [−2, 2]. Dotted vertical white line separate IFN-stimulated and unstimulated samples. d Female–male fold change distribution of MF-ISGs and all remaining genes from unstimulated samples (red and light blue, respectively) and MF-ISGs and all remainder genes from IFN-stimulated samples (green and yellow, respectively). e Box plot presenting female–male log₂ fold change (FC) distribution of the genes in modules C1–C5 defined by Mostafavi et al.³⁵ from IFN-stimulated macrophages. On each box, the central mark indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles, respectively. The whiskers extend to the most extreme data points not considered outliers, and the outliers are plotted individually in red. Unstm unstimulated, IFN interferon. Modules whose distributions are significantly different from zero (one-sample two-sided t test pFDR < 0.05) are marked by asterisk. Source data for a–e are provided as a Source Data file