Chen, Yung-YiSullivan, JackHanley, ShaunPrice, JoshuaTariq, Mohammad AMcIlvenna, Luke CWhitham, MartinSharma-Oates, ArchanaHarrison, PaulLord, Janet MHazeldine, Jon2024-11-052024-11-052024-10-23Chen YY, Sullivan J, Hanley S, Price J, Tariq MA, McIlvenna LC, Whitham M, Sharma-Oates A, Harrison P, Lord JM, Hazeldine J. Impact of Senescent Cell-Derived Extracellular Vesicles on Innate Immune Cell Function. Adv Biol (Weinh). 2024 Dec;8(12):e2400265. doi: 10.1002/adbi.202400265. Epub 2024 Oct 23.2701-019810.1002/adbi.20240026539441562http://hdl.handle.net/20.500.14200/6374Extracellular vesicles (EVs) are components of the senescence-associated secretory phenotype (SASP) that influence cellular functions via their cargo. Here, the interaction between EVs derived from senescent (SEVs) and non-senescent (N-SEVs) fibroblasts and the immune system is investigated. Via endocytosis, SEVs are phagocytosed by monocytes, neutrophils, and B cells. Studies with the monocytic THP-1 cell line find that pretreatment with SEVs results in a 32% (p < 0.0001) and 66% (p < 0.0001) increase in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-α) production when compared to vehicle control or N-SEVs respectively. Interestingly, relative to vehicle control, THP-1 cells exposed to N-SEVs exhibit a 20% decrease in TNF-α secretion (p < 0.05). RNA sequencing reveals significant differences in gene expression in THP-1 cells treated with SEVs or N-SEVs, with vesicle-mediated transport and cell cycle regulation pathways featuring predominantly with N-SEV treatment, while pathways relating to SLITS/ROBO signaling, cell metabolism, and cell cycle regulation are enriched in THP-1 cells treated with SEVs. Proteomic analysis also reveals significant differences between SEV and N-SEV cargo. These results demonstrate that phagocytes and B cells uptake SEVs and drive monocytes toward a more proinflammatory phenotype upon LPS stimulation. SEVs may therefore contribute to the more proinflammatory immune response seen with aging.en© 2024 The Author(s). Advanced Biology published by Wiley‐VCH GmbH.Microbiology. ImmunologyArticle