Fig. 2. Immune and epigenetic mechanisms mediating IL4-induced trained immunity.

a, Schematic overview of previously described premier IL4 signalling pathways¹⁹. Generated using Biorender. b, TNF and IL6 levels after 24 h stimulation of monocytes while blocking key IL4 signalling routes. c, TNF and IL6 levels after re-stimulation of cells that were trained with IL4 while blocking key IL4 signalling routes. d, Heat map of the transcriptome of IL4-trained cells, before and after re-stimulation. e, TF motif enrichment analysis in IL4-trained immunity (heat map indicates z-scores). f, Pathway enrichment analyses of the IL4-trained immunity transcriptome. g, TNF and IL6 levels after re-stimulation of cells that were trained with IL4 in the presence of a SET7 methyltransferase inhibitor. CPH, cyproheptadine. h, ChIP-qPCR AUC analysis of TNF in IL4-trained cells. Data in bar graphs are presented as mean ± s.d.