{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301573/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Methylation profiling"],"species":["Homo sapiens"],"gds_type":["Methylation profiling by genome tiling array"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301573"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Folate Receptor Beta Regulates Macrophage NLRP3 Inflammasome Activation and Pyroptosis in a Folate-Independent Manner [methylation array]","description":"Folate receptor beta (FRb), encoded by FOLR2, is selectively expressed in monocytes and macrophages, yet its function in innate immune signaling remains poorly defined. Here, we identify FRb as a novel regulator of NLRP3 inflammasome activation and pyroptosis in human THP-1 macrophages. Using CRISPR/Cas9-mediated gene deletion, we show that loss of FOLR2 impairs caspase-1 activation, gasdermin D cleavage, and IL-1b release in response to multiple NLRP3 stimuli, without altering pro-IL-1 b induction. These defects were not rescued by exogenous folate and were independent of extracellular folate concentrations. Mechanistically, FOLR2 deletion reduced potassium efflux and downregulated multiple potassium channel genes. Single-cell RNA sequencing revealed broad transcriptional repression in FRb-deficient macrophages, including genes involved in inflammasome signaling and ion transport. Genome-wide methylation profiling showed increased CpG hypermethylation in FOLR2-deficient cells, consistent with reduced transcriptional activity. Our findings indicate that FRb promotes NLRP3 activation in a folate-independent manner by regulating transcription and K⁺ efflux in macrophages. These data reveal a previously unrecognized immunoregulatory role for FRb with implications for host defense, autoimmunity, and macrophage function in tissue microenvironments such as the tumor or placenta.","dates":{"publication":"2026/04/15"},"accession":"GSE301573","cross_references":{"GSM":["GSM9085502","GSM9085500","GSM9085501","GSM9085495","GSM9085498","GSM9085499","GSM9085496","GSM9085497"],"GPL":["33022"],"GSE":["301573"],"taxon":["Homo sapiens"]}}