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Fibroblast orchestration of inflammaging via NF-kB activation (Xenium Analysis)

ABSTRACT: With age mice develop bronchus-associated lymphoid tissue (BALT) and the accumulation of Gzmk+Cd8+ T cells in the lung. We generated a mouse model in which deleting Tnfaip3 (a negative regulator of NF-kB) from fibroblasts in young mice recapitulates many of these age-related changes. Using spatial transcriptomics we identified similarity in the BALT structure formed in normal aging and that which develops in response to fibroblast deletion of Tnfaip3.

ORGANISM(S): Mus musculus

PROVIDER: GSE286085 | GEO | 2025/12/04

REPOSITORIES: GEO

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

Project description: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).

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Fibroblast orchestration of inflammaging via NF-kB activation (Lung Resident CD45+ cell and fibroblast analysis)

Project description:In this study we used scRNA-sequencing to compare lung resident CD45+ cells and bulk RNA-sequencing to compare lung PDGFRa+ fibroblasts from 2-month-old mice in which the NF-kB inhibitor Tnfaip3 has been deleted from fibroblasts (D1cA20) with control mice (A20control). We identified enrichment of Gzmk+CD8+ T cells in the D1cA20 relative to control mice. As a follow-up to this initial study we used bulk RNA sequencing to compare the transcriptomes of lung adventitial fibroblasts from 4-month C57BL/6 (Young B6), 21-month C57BL/6 (Aged B6), 4-month Tnfaip3 f/f (Tnfaip3 Control) and 4-month Dermo1-cre;Tnfaip3f/f (Tnfaip3 CKO/D1cA20) mice. We identified that aged B6 adventitial fibroblasts share transcriptional similarity with those from young Tnfaip3 CKO mice. Pathway analysis revealed NF-kB to be significantly upregulated in both Aged B6 and Tnfaip3 CKO relative to Young B6 or Tnfaip3 control.

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Fibroblast orchestration of inflammaging via NF-kB activation (Xenium Analysis)

Project description:Fibroblast orchestration of inflammaging via NF-kB activation (Xenium Analysis)

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Time series of murine lungs after flu infection

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Fibroblast orchestration of inflammaging via NF-kB activation (Aged vs Young Lung Fibroblasts and Epithelium)

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Radioresistant Cells in STING Gain-of-function Mice Initiate Lymphocyte-dependent Lung Inflammation and IFNγ-dependent Mortality

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

Project description:Fibroblast orchestration of inflammaging via NF-kB activation (CD3+ T cell, TCR)

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