Fig. 3: Characteristic roles of JAK-STAT signaling in homeostasis.

a, Differential gene expression for IRF9 and STAT2 knockouts. Left, scatterplot of log₂FCs for the two knockouts relative to matched wild-type samples. Right, bar plots of differential expression levels relative to wild type for selected genes, displaying mean and standard error. b, Differential gene expression for STAT5 modulation and IL-2 treatment in T cells. Left, scatterplot of log₂FCs for the hyperactivated STAT5B^N642H mutant (STAT5-hyp) and STAT5 knockout relative to wild type, and for the response of wild-type T cell to in vitro IL-2 treatment at two time points. Right, gene set enrichment analysis for the differentially expressed genes (two-sided Fisher’s exact test, corrected for multiple comparisons). Upregulation, downregulation and no change are indicated by ‘+’, ‘−’ and ‘o’, respectively. c, Differential gene expression for STAT1 isoforms. Left, scatterplot of log₂FCs for the two STAT1 isoforms and for the full STAT1 knockout. Right, box plots showing STAT1 isoform effects (log₂FC) for genes with significant STAT1 effect in macrophages, grouped by the effects of full STAT1 and STAT2 knockouts. Upregulation, downregulation and no change are indicated by a ‘+’, ‘−’ and ‘o’, respectively. Box plots show the full data range, with the box indicating interquartile range and median. Bottom, bar plots showing the expression levels of selected genes affected by these mutants. d, Differential gene expression for TYK2 modulation. Left, scatterplot of log₂FCs for the TYK2 knockout and the kinase-dead TYK2^K923E mutant. Right, TYK2 mutant effects on selected IL-12 regulated genes (two-sided linear mixed models, corrected for multiple comparisons). Bottom, bar plots showing the expression levels of selected genes affected by these mutants. Mac, macrophage; r, Spearman correlation coefficient. Bar plots display the mean and standard error.