{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE281nnn/GSE281099/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":[" Genome binding/occupancy profiling by high throughput sequencing","Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281099"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Deletion of a Distal IRF4 Element Prevents Inflammation-induced Reprogramming of Human Regulatory T-cell Fate","description":"Adoptive regulatory T cell (Treg) therapy is an emergent treatment paradigm in which ex vivo-expanded Tregs are administered to promote immune tolerance in transplant and autoimmune disease patients. While preclinical models have demonstrated remarkable efficacy, lineage-tracing studies have also revealed that chronic inflammatory exposures can cause a subset of murine Tregs to undergo Foxp3 downregulation and epigenetic reprogramming toward a dysfunctional, proinflammatory state. Despite the potential ramifications for clinical translation, whether human Tregs exhibit a similar susceptibility to inflammatory cytokine-mediated lineage decommitment remains inconclusive. Here, we present an in vitro model of human Treg destabilization characterized by FOXP3 downregulation, Treg-specific demethylated region (TSDR) re-methylation, loss of suppressive activity, and gain of proinflammatory functions. Analysis of single-cell ATAC and transcriptomic profiles from destabilized Tregs revealed a switch in chromatin accessibility between two elements at the IRF4 locus. Excision of the distal IRF4 element enabled Tregs to resist inflammatory cytokine-induced reprogramming, presenting a potential strategy to design more effective Treg therapies.","dates":{"publication":"2026/08/05"},"accession":"GSE281099","cross_references":{"GSM":["GSM8610860","GSM8610861","GSM8610862","GSM8610863","GSM8610870","GSM8610868","GSM8610857","GSM8610858","GSM8610869","GSM8610859","GSM8610864","GSM8610865","GSM8610855","GSM8610866","GSM8610856","GSM8610867"],"GPL":["24676"],"GSE":["281099"],"taxon":["Homo sapiens"]}}