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Cited by 25Extracellular vesicles in diseaseInfluenza Virus Research StudiesRespiratory Support and Mechanisms

Mitigation of influenza-mediated inflammation by immunomodulatory matrix-bound nanovesicles

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Crum, Raphael J., Huckestien, Brydie R., Dwyer, Gaelen, Mathews, Lisa, Nascari, David G., Hussey, George S., Turnquist, Heth R., Alcorn, John F. +1 more·2023·Science Advances
DOI 10.1126/sciadv.adf9016PMC PMC10198633
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Abstract

Cytokine storm describes a life-threatening, systemic inflammatory syndrome characterized by elevated levels of proinflammatory cytokines and immune cell hyperactivation associated with multi-organ dysfunction. Matrix-bound nanovesicles (MBV) are a subclass of extracellular vesicle shown to down-regulate proinflammatory immune responses. The objective of this study was to assess the efficacy of MBV in mediating influenza-induced acute respiratory distress syndrome and cytokine storm in a murine model. Intravenous administration of MBV decreased influenza-mediated total lung inflammatory cell density, proinflammatory macrophage frequencies, and proinflammatory cytokines at 7 and 21 days following viral inoculation. MBV decreased long-lasting alveolitis and the proportion of lung undergoing inflammatory tissue repair at day 21. MBV increased the proportion of activated anti-viral CD4 + and CD8 + T cells at day 7 and memory-like CD62L + CD44 + , CD4 + , and CD8 + T cells at day 21. These results show immunomodulatory properties of MBV that may benefit the treatment of viral-mediated pulmonary inflammation with applicability to other viral diseases such as SARS-CoV-2.

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Cited by

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Authors
Crum, R. J., Huckestien, B. R., Dwyer, G., Mathews, L., Nascari, D. G., Hussey, G. S., Turnquist, H. R., Alcorn, J. F., & Badylak, S. F.
Affiliations
University of Pittsburgh (US)
Corresponding author
Badylak, Stephen F.
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2023-05-19
Volume
9
Issue
20
Pages
eadf9016-eadf9016
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.adf9016
PMC
PMC10198633
OpenAlex
W4377088195
Cited by
25
References
4
Citations by year
2026: 6 · 2025: 9 · 2024: 8 · 2023: 2
FWCI
2.23
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science Advances (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Defense (W81XWH-21, W81XWH)
  • University of Pittsburgh (W81XWH-21-1-0894)
  • National Institutes of Health (W81XWH)
  • National Heart, Lung, and Blood Institute (R01HL107380, R01HL122489)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR073527)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
Keywords
influenza, cytokine storm, acute respiratory distress syndrome, lung inflammation, extracellular vesicles, immunomodulation, macrophages, inflammatory cytokines, alveolitis, T cell activation, memory T cells, SARS-CoV-2
MeSH terms
Cytokine Release Syndrome, COVID-19, SARS-CoV-2, Animals, Humans, Immunity, Inflammation, Influenza, Human, Cytokines, CD8-Positive T-Lymphocytes, Mice

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