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Fibroblast orchestration of inflammaging via NF-kB activation (CD3+ T cell, CD8+ T cell)

GSE286324 Mus musculus Expression profiling by high throughput sequencing; Other 6 samples Submitted 2025/12/04 Platform GPL24247Platform GPL34290
Summary
Aging is associated with the accumulation of Gzmk+CD8+ T cells in the blood and multiple tissues that have features of exhaustion. We have found that by genetically activating NF-kB in fibroblasts (though the deletion of the NF-kB inhibitor Tnfaip3 with the pan-fibroblast Dermo1-cre, Tnfaip3 CKO) we are able to recapitulate this age-related accumulation of Gzmk+CD8+ T cells in the lungs of young mice. We additionally generated a Gzmk reporter mouse (GATOR) that allows the identification and isolation of these cells via tdTomato expression. In the first study associated with this record, we used scRNA and TCR sequencing to compare lung resident CD3+ T cells from young Tnfaip3 CKO mice with those from young control and aged wild-type mice. As a follow-up to this initial study we utilized scRNAseq to compare the transcriptome and TCRs of lung resident Gzmk+ CD8+ T cells from aged WT mice, young Tnfaip3 CKO;GATOR mice, and young GATOR mice chronically infected with LCMV clone 13 (as a "gold standard" for T cell exhaustion).
Published in
Fibroblast orchestration of inflammaging via NF-kB activation
Allen NC, Ringler C, Lee JY et al. · bioRxiv : the preprint server for biology 2025 · PMID 41256682 · doi:10.1101/2025.10.01.679697
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Also filed as BioProject PRJNA1208923 and SRA study SRP556593. Searching any of these in the dataset finder brings you back here.

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