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Immune system-related plasma extracellular vesicles in healthy aging.

Publication ,  Journal Article
Zhang, X; Ma, S; Huebner, JL; Naz, SI; Alnemer, N; Soderblom, EJ; Aliferis, C; Kraus, VB
Published in: Front Immunol
2024

OBJECTIVES: To identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults. METHODS: EV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial freeze-thaws each); validation by high-resolution flow cytometry and EV cytokine quantification by multiplex ELISA (n=28 healthy donors, aged 18-83 years); quantification of WI-38 fibroblast cell proliferation response to co-culture with PKH67-labeled young and old plasma EVs. The EV samples from these plasma specimens were previously characterized for bilayer structure, intra-vesicle mitochondria and cytokines, and hematopoietic cell-related surface markers. RESULTS: Compared with matched exo-EVs (EV-depleted supernatants), endo-EVs (EV-associated) had higher mean TNF-α and IL-27, lower mean IL-6, IL-11, IFN-γ, and IL-17A/F, and similar mean IL-1β, IL-21, and IL-22 concentrations. Some endo-EV and exo-EV cytokine concentrations were correlated, including TNF-α, IL-27, IL-6, IL-1β, and IFN-γ, but not IL-11, IL-17A/F, IL-21 or IL-22. Endo-EV IFN-γ and exo-EV IL-17A/F and IL-21 declined with age. By proteomics and confirmed by flow cytometry, we identified age-associated decline of fibrinogen (FGA, FGB and FGG) in EVs. Age-related EV proteins indicated predominant origins in the liver and innate immune system. WI-38 cells (>95%) internalized similar amounts of young and old plasma EVs, but cells that internalized PKH67-EVs, particularly young EVs, underwent significantly greater cell proliferation. CONCLUSION: Endo-EV and exo-EV cytokines function as different biomarkers. The observed healthy aging EV phenotype reflected a downregulation of EV fibrinogen subpopulations consistent with the absence of a pro-coagulant and pro-inflammatory condition common with age-related disease.

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Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2024

Volume

15

Start / End Page

1355380

Location

Switzerland

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Organic Chemicals
  • Interleukin-6
  • Interleukin-27
  • Interleukin-17
  • Immune System
  • Humans
  • Healthy Aging
  • Fibrinogen
  • Extracellular Vesicles
 

Citation

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Zhang, X., Ma, S., Huebner, J. L., Naz, S. I., Alnemer, N., Soderblom, E. J., … Kraus, V. B. (2024). Immune system-related plasma extracellular vesicles in healthy aging. Front Immunol, 15, 1355380. https://doi.org/10.3389/fimmu.2024.1355380
Zhang, Xin, Sisi Ma, Janet L. Huebner, Syeda Iffat Naz, Noor Alnemer, Erik J. Soderblom, Constantin Aliferis, and Virginia Byers Kraus. “Immune system-related plasma extracellular vesicles in healthy aging.Front Immunol 15 (2024): 1355380. https://doi.org/10.3389/fimmu.2024.1355380.
Zhang X, Ma S, Huebner JL, Naz SI, Alnemer N, Soderblom EJ, et al. Immune system-related plasma extracellular vesicles in healthy aging. Front Immunol. 2024;15:1355380.
Zhang, Xin, et al. “Immune system-related plasma extracellular vesicles in healthy aging.Front Immunol, vol. 15, 2024, p. 1355380. Pubmed, doi:10.3389/fimmu.2024.1355380.
Zhang X, Ma S, Huebner JL, Naz SI, Alnemer N, Soderblom EJ, Aliferis C, Kraus VB. Immune system-related plasma extracellular vesicles in healthy aging. Front Immunol. 2024;15:1355380.

Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2024

Volume

15

Start / End Page

1355380

Location

Switzerland

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Organic Chemicals
  • Interleukin-6
  • Interleukin-27
  • Interleukin-17
  • Immune System
  • Humans
  • Healthy Aging
  • Fibrinogen
  • Extracellular Vesicles