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Airway epithelial hyperactivation of JAK-STAT signaling impairs type-III IFN responses during RSV infection in Down Syndrome [Bulk RNA-seq]

GSE271245 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2025/12/12 Platform GPL24676
Summary
Trisomy 21 (TS21), commonly known as Down syndrome (DS), increases mortality risk due to respiratory syncytial virus (RSV) in children by nearly 9-fold. Interferon (IFN)-mediated JAK/STAT antiviral signaling is altered in DS given that four IFN receptor genes reside on chromosome 21. This study unveils an interferonopathy in TS21 pediatric airway epithelial cells (AECs), the primary point of entry and defense against RSV. Relative to euploid cells, TS21 AECs show reduced RSV infection levels accompanied by baseline hyperactivation of IFNJAK/STAT antiviral signaling. Conversely, in response to RSV infection, both the induction of IFN signaling and type-III IFN production are reduced in TS21 AECs compared to controls. JAK inhibition mitigates baseline IFN hyperactivation and increases type-III IFN antiviral response in TS21 AECs. Our findings identify hyperactivation of IFN-JAK/STAT in AECs of children with DS as a potentially targetable mechanism for reducing the lethal impact of RSV infection in this vulnerable population.
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Direct links to NCBI, no account and no request form: the whole study as GSE271245_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1130514 and SRA study SRP517324. Searching any of these in the dataset finder brings you back here.

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