Fig. 3. A core inflammation program is conserved across mouse and human neutrophils.

a Overview of the 11 studies integrated for analysis. Differential expression testing was performed independently for each study, resting neutrophils within each study were used as control. b A combined analysis of the neutrophil response to activation/inflammation identifies 179 consistently upregulated (core inflammation program) and 42 downregulated genes in inflammation. Shown are all (N = 9697) tested genes ranked by their −log₁₀ Benjamini-Hochberg adjusted Fisher P-value (adjusted Fisher’s combined test on two-sided P-values from individual differential expression analyses for each comparison). The 500 genes with the lowest P-values were subjected to an additional filtering step based on a log₂ fold change cutoff ≥0.5 and ≤−0.5 for upregulated and downregulated genes. Highlighted (IL4R, CD14, CD69, CD274, CD40) upregulated genes were validated experimentally (Figs. 6 and 7). c 42 genes downregulated in inflammation and 179 core inflammation genes are shared across studies. Shown are the log₂ fold changes across comparisons of genes up- and downregulated in inflammation. Rows represent a comparison, columns represent genes that passed our meta-analysis thresholds. Columns are arranged by the mean log₂ fold change across all comparisons. For each direction, the 15 genes with the highest absolute log₂ fold change are labeled, as well as genes encoding for proteins validated in Figs. 6 and 7. d Core inflammation genes are not expressed in resting neutrophils in both species and are induced upon activation. Shown is a heatmap with relative expression values (z-score for each gene across samples) of the core inflammation genes. Each column represents a gene, and each row a sample. P-values: Results of a Benjamini-Hochberg adjusted Fisher’s combined test. We labeled the top 20 genes with the lowest P-values, genes that were also labeled in (c), and manually labeled TRAF1 and JUNB. e Conserved Gene Set Enrichment Analysis based on rankings derived from each comparison’s log₂ fold changes. Heatmap showing normalized enrichment scores. Only pathways that have been significant in more than 50% of comparisons are depicted. Gray fields indicate nonsignificant NES values. Source data are provided as a Source Data file.