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

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.