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Sci Adv . Mitigation of influenza-mediated inflammation by immunomodulatory matrix-bound nanovesicles

tetano

Editor, Senior Moderator
Sci Adv


. 2023 May 19;9(20):eadf9016.
doi: 10.1126/sciadv.adf9016. Epub 2023 May 19. Mitigation of influenza-mediated inflammation by immunomodulatory matrix-bound nanovesicles

Raphael J Crum[SUP] 1 [/SUP], Brydie R Huckestien[SUP] 2 3 [/SUP], Gaelen Dwyer[SUP] 3 4 5 [/SUP], Lisa Mathews[SUP] 3 4 5 [/SUP], David G Nascari[SUP] 1 [/SUP], George S Hussey[SUP] 1 6 [/SUP], Heth R Turnquist[SUP] 1 3 4 5 [/SUP], John F Alcorn[SUP] 2 3 [/SUP], Stephen F Badylak[SUP] 1 5 6 7 [/SUP]



Affiliations
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells at day 7 and memory-like CD62L[SUP]+[/SUP] CD44[SUP]+[/SUP], CD4[SUP]+[/SUP], and CD8[SUP]+[/SUP] 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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