{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318453/"]},"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=GSE318453"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"IL-15 Signaling During a Critical NK Cell Developmental Window Subverts Maturation and KIR Acquisition [Methylation array]","description":"Natural killer (NK) cells are key mediators of immune surveillance following hematopoietic stem cell transplantation (HSCT). However, despite the known post-conditioning spike in interleukin-15 (IL-15), NK cell maturation is frequently delayed following HSCT. We found that during in vitro NK cell development from CD34+ hematopoietic progenitor cells (HPCs), early exposure to IL-15 drove aberrant mTOR activation, resulting in epigenetic and transcriptional dysregulation and suppressed maturation and KIR acquisition. In contrast, transiently withholding IL-15 or blocking mTOR with rapamycin produced NK cell developmental intermediates intrinsically poised to mature into highly functional, KIR-expressing NK cells. Single-cell analysis of HSCT patients at early time points post-transplant revealed a similar aberrant transcriptional signature of IL-15/mTOR overactivation in circulating donor-derived NK cells. These findings define a developmental window during which IL-15 signaling can paradoxically subvert NK cell maturation and KIR acquisition, suggesting that temporally regulated cytokine signaling could accelerate immune reconstitution and improve therapeutic efficacy.","dates":{"publication":"2026/08/21"},"accession":"GSE318453","cross_references":{"GSM":["GSM9495183","GSM9495184","GSM9495140","GSM9495141","GSM9495185","GSM9495186","GSM9495142","GSM9495180","GSM9495181","GSM9495182","GSM9495147","GSM9495148","GSM9495149","GSM9495187","GSM9495143","GSM9495144","GSM9495188","GSM9495189","GSM9495145","GSM9495146","GSM9495194","GSM9495150","GSM9495195","GSM9495151","GSM9495152","GSM9495196","GSM9495197","GSM9495153","GSM9495190","GSM9495191","GSM9495192","GSM9495193","GSM9495158","GSM9495159","GSM9495198","GSM9495154","GSM9495155","GSM9495199","GSM9495156","GSM9495157","GSM9495161","GSM9495162","GSM9495163","GSM9495164","GSM9495160","GSM9495169","GSM9495165","GSM9495166","GSM9495167","GSM9495168","GSM9495172","GSM9495173","GSM9495174","GSM9495175","GSM9495170","GSM9495171","GSM9495136","GSM9495137","GSM9495138","GSM9495139","GSM9495176","GSM9495177","GSM9495178","GSM9495134","GSM9495135","GSM9495179"],"GPL":["21145","33022"],"GSE":["318453"],"taxon":["Homo sapiens"]}}