GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE252nnn/GSE252661/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE252661GEOGSEfalseIL-4 Exploits TNF signaling to Shape Its Signature Gene Expression in Human Monocytes. [ATAC-Seq]Investigation of crosstalk between antagonistic pro- and anti-inflammatory cytokines has focused on mechanisms and functional consequences of cross-inhibition. We investigated cross-regulation between proinflammatory TNF and anti-inflammatory IL-4 in primary human monocytes and in a skin wound-healing model. Surprisingly, TNF functioned mainly as a costimulator of IL-4-induced gene expression, whereas IL-4 selectively inhibited the TNF-induced IFN response, leaving inflammatory gene expression mostly intact. TNF and IL-4 synergistically induced gene sets important for regulating inflammation and tissue repair, which were highly induced during the phase of wound healing when these cytokines are co-expressed. Crosstalk between TNF and IL-4 was mediated by epigenetic chromatin-mediated mechanisms associated with cooperation between NF-κB and STAT6 transcription factors, erasure of negative histone mark H3K27me3, and selective inhibition of IRF1. These results identify a long-sought mechanism for expansion of the IL-4 response, and highlight the complexity of crosstalk between antagonistic cytokines that includes cooperation for select gene responses important in immune response and tissue repair.2026/09/03GSE252661GSM8004907GSM8004918GSM8004928GSM8004906GSM8004917GSM8004916GSM8004905GSM8004927GSM8004926GSM8004915GSM8004909GSM8004919GSM8004908GSM8004921GSM8004910GSM8004920GSM8004925GSM8004914GSM8004924GSM8004913GSM8004912GSM8004923GSM8004922GSM800491120301252661Homo sapiens