{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE252nnn/GSE252661/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE252661"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"IL-4 Exploits TNF signaling to Shape Its Signature Gene Expression in Human Monocytes. [ATAC-Seq]","description":"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.","dates":{"publication":"2026/09/03"},"accession":"GSE252661","cross_references":{"GSM":["GSM8004907","GSM8004918","GSM8004928","GSM8004906","GSM8004917","GSM8004916","GSM8004905","GSM8004927","GSM8004926","GSM8004915","GSM8004909","GSM8004919","GSM8004908","GSM8004921","GSM8004910","GSM8004920","GSM8004925","GSM8004914","GSM8004924","GSM8004913","GSM8004912","GSM8004923","GSM8004922","GSM8004911"],"GPL":["20301"],"GSE":["252661"],"taxon":["Homo sapiens"]}}