Fig. 4: Absence of TYK2 or its kinase activity alters the transcriptome of skin-infiltrating myeloid cells.

a WT, Tyk2^-/- and Tyk2^K923E mice were infected as described in the legend to Fig. 1. RNA from skin-sorted CD45⁺CD3^-CD19^-NK1.1^- myeloid cells was isolated for subsequent RNA-sequencing. b Volcano plots showing the differentially expressed genes between Tyk2^-/- and WT and Tyk2^K923E and WT cells. Genes were identified from DESeq2-normalized read counts of genes with a threshold of padj < 0.05 between Tyk2^-/- and WT and Tyk2^K923E and WT cells. Data are from one experiment (n = 3 mice per genotype). c Heatmap showing the differentially expressed genes between WT and TYK2-mutant cells with an absolute log2-fold change > 1 (padj <0.05). IFN-stimulated genes (ISGs) are highlighted in orange. d Pathway analysis of deregulated pathways between WT and ^Tyk2-/- cells was performed using Reactome. The top 10 upregulated and downregulated pathways are shown. e mRNA levels of Ifng in the infected skin on day 4 p.i were measured by RT-qPCR. Data were normalized to the housekeeping gene Ube2d2. Pooled data from 2 independent experiments are shown and mean values ± SEM are given; PBS: n = 2/genotype; C. albicans: n = 12 (WT), n = 7 (Tyk2^-/-) and n = 9 (Tyk2^K923E); n.d not detectable; n: biological replicates. f IFNγ in the skin on day 2 p.i was measured using a Luminex assay. Pooled data from 2 independent experiments are shown. Mean values ± SEM are given; PBS: n = 2/genotype; C. albicans: n = 8 (WT) and n = 9 (Tyk2^-/-, Tyk2^K923E); n.d, not detectable; n: biological replicates. Statistical analysis was conducted using One-way ANOVA followed by Tukey’s multiple comparison test and statistical significance is only given for the comparison between the genotypes (e, f). Source data are provided as a Source Data file.