Impact of senescent cell-derived extracellular vesicles on innate immune cell function
Chen, Yung-Yi Sullivan, Jack Hanley, Shaun Price, Joshua Tariq, Mohammad A McIlvenna, Luke C Whitham, Martin Sharma-Oates, Archana Harrison, Paul Lord, Janet M
Chen, Yung-Yi
Sullivan, Jack
Hanley, Shaun
Price, Joshua
Tariq, Mohammad A
McIlvenna, Luke C
Whitham, Martin
Sharma-Oates, Archana
Harrison, Paul
Lord, Janet M
Abstract
Extracellular 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.
MIDER Authors
Affiliations
University of Birmingham; University Hospitals Birmingham NHS Foundation Trust
Citations
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Date
2024-10-23
Type
Article
Subject
Collections
Citation
Chen 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.