{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330551/"]},"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=GSE330551"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Th2-primed innate immune amplification defines a distinct atopic dermatitis endotype","description":"Atopic dermatitis (AD) is clinically heterogeneous, but reproducible molecular endotypes remain incompletely defined. By integrating >1,300 lesional and non-lesional skin transcriptomes from 30 studies, we identified two robust AD endotypes that share a conserved lesional core program of barrier disruption and type 2 activation. In contrast to endotype 1 (62%), endotype 2 (38%) was distinguished by a compact 108-gene innate-inflammatory signature (including IL1B and IL6), increased myeloid infiltration, and Staphylococcus aureus-associated dysbiosis. Endotype assignment was stable across longitudinal datasets, with only limited, non-systematic switching upon systemic treatment. Analysis of trial and observational data provided preliminary evidence for lower clinical response and higher residual molecular activity under dupilumab in endotype 2 compared to endotype 1. Interaction modeling of Th2 and innate module activity revealed a Th2-amplified innate state that predicts endotype 2, paralleling functional experiments in which IL-1b/IL-6 synergize with Th2 cytokines to exacerbate keratinocyte inflammation and to impair keratinocyte differentiation. Our findings offer new insights into the biological diversity of AD and establish a robust foundation for mechanistic stratification, with implications for therapeutic strategies.","dates":{"publication":"2026/05/13"},"accession":"GSE330551","cross_references":{"GSM":["GSM9728680","GSM9728682","GSM9728681","GSM9728684","GSM9728683","GSM9728686","GSM9728685","GSM9728688","GSM9728600","GSM9728721","GSM9728720","GSM9728687","GSM9728602","GSM9728723","GSM9728689","GSM9728601","GSM9728722","GSM9728604","GSM9728725","GSM9728603","GSM9728724","GSM9728606","GSM9728727","GSM9728605","GSM9728726","GSM9728608","GSM9728729","GSM9728728","GSM9728607","GSM9728609","GSM9728691","GSM9728690","GSM9728693","GSM9728692","GSM9728695","GSM9728694","GSM9728697","GSM9728730","GSM9728696","GSM9728611","GSM9728732","GSM9728699","GSM9728731","GSM9728698","GSM9728610","GSM9728734","GSM9728613","GSM9728612","GSM9728733","GSM9728615","GSM9728736","GSM9728614","GSM9728735","GSM9728617","GSM9728738","GSM9728737","GSM9728616","GSM9728619","GSM9728618","GSM9728739","GSM9728660","GSM9728662","GSM9728661","GSM9728664","GSM9728663","GSM9728666","GSM9728665","GSM9728668","GSM9728701","GSM9728700","GSM9728667","GSM9728703","GSM9728669","GSM9728702","GSM9728705","GSM9728704","GSM9728707","GSM9728706","GSM9728709","GSM9728708","GSM9728671","GSM9728670","GSM9728673","GSM9728672","GSM9728675","GSM9728674","GSM9728677","GSM9728710","GSM9728676","GSM9728712","GSM9728679","GSM9728711","GSM9728678","GSM9728714","GSM9728713","GSM9728716","GSM9728715","GSM9728718","GSM9728717","GSM9728719","GSM9728640","GSM9728761","GSM9728760","GSM9728763","GSM9728642","GSM9728641","GSM9728762","GSM9728644","GSM9728643","GSM9728646","GSM9728645","GSM9728648","GSM9728647","GSM9728649","GSM9728651","GSM9728650","GSM9728653","GSM9728652","GSM9728655","GSM9728654","GSM9728657","GSM9728656","GSM9728659","GSM9728658","GSM9728620","GSM9728741","GSM9728740","GSM9728622","GSM9728743","GSM9728621","GSM9728742","GSM9728624","GSM9728745","GSM9728623","GSM9728744","GSM9728626","GSM9728747","GSM9728625","GSM9728746","GSM9728628","GSM9728749","GSM9728748","GSM9728627","GSM9728629","GSM9728590","GSM9728592","GSM9728591","GSM9728594","GSM9728593","GSM9728750","GSM9728596","GSM9728595","GSM9728631","GSM9728752","GSM9728598","GSM9728751","GSM9728597","GSM9728630","GSM9728754","GSM9728633","GSM9728632","GSM9728753","GSM9728599","GSM9728635","GSM9728756","GSM9728634","GSM9728755","GSM9728637","GSM9728758","GSM9728757","GSM9728636","GSM9728639","GSM9728759","GSM9728638"],"GPL":["18573"],"GSE":["330551"],"taxon":["Homo sapiens"]}}