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

ABSTRACT: 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).

ORGANISM(S): Mus musculus

PROVIDER: GSE286324 | GEO | 2025/12/04

REPOSITORIES: GEO

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