{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:09:56Z","timestamp":1792199396218,"version":"4.4.0"},"reference-count":61,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"20","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,5,19]]},"abstract":"<jats:p>\n            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\n            <jats:sup>+<\/jats:sup>\n            and CD8\n            <jats:sup>+<\/jats:sup>\n            T cells at day 7 and memory-like CD62L\n            <jats:sup>+<\/jats:sup>\n            CD44\n            <jats:sup>+<\/jats:sup>\n            , CD4\n            <jats:sup>+<\/jats:sup>\n            , and CD8\n            <jats:sup>+<\/jats:sup>\n            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.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adf9016","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T17:58:22Z","timestamp":1684519102000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":27,"title":["Mitigation of influenza-mediated inflammation by immunomodulatory matrix-bound nanovesicles"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8597-1874","authenticated-orcid":true,"given":"Raphael J.","family":"Crum","sequence":"first","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brydie R.","family":"Huckestien","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaelen","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Thomas E.\u00a0Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Thomas E.\u00a0Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Nascari","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5636-0994","authenticated-orcid":true,"given":"George S.","family":"Hussey","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4173-4014","authenticated-orcid":true,"given":"Heth R.","family":"Turnquist","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Thomas E.\u00a0Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Alcorn","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3555-0689","authenticated-orcid":true,"given":"Stephen F.","family":"Badylak","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028680"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01708"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.763292"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1051-9"},{"key":"e_1_3_3_7_2","first-page":"327","article-title":"Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by 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