{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE310nnn/GSE310965/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310965"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Islet-Intrinsic Sex Differences in Inflammatory Signaling Contribute to Autoimmune Diabetes Susceptibility","description":"Whereas most autoimmune diseases exhibit female predominance, type 1 diabetes (T1D) occurs more frequently in males after puberty, suggesting a role for sex hormones in disease modification. Because islet β cells actively shape local immune responses, we hypothesized that sex-specific islet responses to inflammation contribute to this disparity. Using transcriptomic and proteomic analyses of human islets from male and female donors, we found that male islets exhibited a more aggressive response to proinflammatory cytokines, characterized by greater induction of interferon signaling and suppression of developmental signaling compared to female islets. Treatment of human islets and mouse β cells with the sex hormone 17β-estradiol (E2) suppressed inflammatory signaling and markers of β-cell maturity while enhancing developmental gene programs. Complementary studies in non-obese diabetic (NOD) mice showed that E2 treatment reduced diabetes incidence and limited progression to severe insulitis. Islet single-cell RNA sequencing revealed that E2 treatment of NOD mice suppressed interferon signaling, chemokine production, and antigen presentation in β cells, while reducing activation and cytotoxicity pathways in immune cells. In an aggressive adoptive transfer model, E2 pretreatment of the recipient mice attenuated hyperglycemia. These findings support a model in which estradiol-mediated β-cell reprogramming reduces β-cell immunogenicity and promotes local immune tolerance, offering mechanistic insight into sex-biased T1D susceptibility.","dates":{"publication":"2026/05/17"},"accession":"GSE310965","cross_references":{"GSM":["GSM9313358","GSM9313357","GSM9313359","GSM9313398","GSM9313354","GSM9313353","GSM9313397","GSM9313356","GSM9313355","GSM9313350","GSM9313394","GSM9313393","GSM9313352","GSM9313396","GSM9313395","GSM9313351","GSM9313390","GSM9313392","GSM9313391","GSM9313369","GSM9313368","GSM9313365","GSM9313364","GSM9313367","GSM9313366","GSM9313361","GSM9313360","GSM9313363","GSM9313362","GSM9313339","GSM9313379","GSM9313376","GSM9313375","GSM9313378","GSM9313377","GSM9313372","GSM9313371","GSM9313374","GSM9313373","GSM9313370","GSM9313347","GSM9313346","GSM9313349","GSM9313348","GSM9313343","GSM9313387","GSM9313386","GSM9313342","GSM9313389","GSM9313345","GSM9313388","GSM9313344","GSM9313383","GSM9313382","GSM9313341","GSM9313385","GSM9313384","GSM9313340","GSM9313381","GSM9313380"],"GPL":["34281"],"GSE":["310965"],"taxon":["Homo sapiens"]}}