GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330551/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330551GEOGSEfalseTh2-primed innate immune amplification defines a distinct atopic dermatitis endotypeAtopic 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.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 sapiens