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- W4313408031 abstract "Abstract Periodontitis (PD) is a chronic inflammatory disease of aging or inflammaging that affects 70.1% of Americans 65 years and older. Age related immunosenescence is implicated in chronic inflammation and impaired immune surveillance, but role in PD is unclear. The aim of this study was to determine cellular mechanisms of immunosenescence in PD in-vivo. Variables including age, bacterial infection with key stone oral pathogen, Porphyromonas gingivalis (Pg), and senolytic agent rapamycin (Rap) were assessed for influence on ligature accelerated PD in young (2–3 mo) and old (24 mo) B6 mice (n=30). Senescence profiling of gingiva and lymph node (LN) was performed by confocal microscopy, flow cytometry and qPCR. Increased SA-BGal, p16 INK4A, p21Waf1/Clip1, CD57+CD28− T cell, Th17/Treg ratio and IL6/TNFa/IL1b were observed in DCs and T cells in gingiva and/or LN as a function of advanced age, or exposure of young mice to Pg gavage. This was associated with a significant increase in bone loss shown by micro CT 3D analysis which was abrogated by Rap. In-vitro analysis revealed a~2-fold increase in secreted exosomes from DCs infected with Pg (PgDCexo). These exosomes were enriched in age-related, anti-apoptosis/anti-autophagy miRNAs, Pg fimbrial adhesin protein mfa1, and IL6/TNFa/IL1b. PgDCexo were injected intragingivally in young mice promoting a premature senescence profile in the gingiva and LN and inflammatory bone loss compared to exosomes from uninfected DCs. We conclude that advanced age and microbially-induced immunosenescence contribute to the pathogenesis of inflammatory bone loss in mice which can be inhibited by rapamycin. P. gingivalis-induced exosomes in dendritic cells promote paracrine senescence of normal bystander cells." @default.
- W4313408031 created "2023-01-06" @default.
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- W4313408031 date "2022-05-01" @default.
- W4313408031 modified "2023-09-25" @default.
- W4313408031 title "Microbially-induced exosomes in dendritic cells promote paracrine immunosenescence: Novel mechanism of inflammatory alveolar bone loss in mice" @default.
- W4313408031 doi "https://doi.org/10.4049/jimmunol.208.supp.171.18" @default.
- W4313408031 hasPublicationYear "2022" @default.
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