Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/162798
Title: Mechanism for the attenuation of neutrophil and complement hyperactivity by MSC exosomes
Authors: Loh, Jia Tong
Zhang, Bin
Teo, Joey Kay Hui
Lai, Ruenn Chai
Choo, Andre Boon Hwa
Lam, Kong-Peng
Lim, Sai Kiang
Keywords: Science::Biological sciences
Science::Medicine
Issue Date: 2022
Source: Loh, J. T., Zhang, B., Teo, J. K. H., Lai, R. C., Choo, A. B. H., Lam, K. & Lim, S. K. (2022). Mechanism for the attenuation of neutrophil and complement hyperactivity by MSC exosomes. Cytotherapy, 24(7), 711-719. https://dx.doi.org/10.1016/j.jcyt.2021.12.003
Project: H19H6a0026
TEx2Pharm
Journal: Cytotherapy
Abstract: Complements and neutrophils are two key players of the innate immune system that are widely implicated as drivers of severe COVID-19 pathogenesis, as evident by the direct correlation of respiratory failure and mortality with elevated levels of terminal complement complex C5b-9 and neutrophils. In this study, we identified a feed-forward loop between complements and neutrophils that could amplify and perpetuate the cytokine storm seen in severe SARS-CoV-2-infected patients. We observed for the first time that the terminal complement activation complex C5b-9 directly triggered neutrophil extracellular trap (NET) release and interleukin (IL)-17 production by neutrophils. This is also the first report that the production of NETs and IL-17 induced by C5b-9 assembly on neutrophils could be abrogated by mesenchymal stem cell (MSC) exosomes. Neutralizing anti-CD59 antibodies abolished this abrogation. Based on our findings, we hypothesize that MSC exosomes could alleviate the immune dysregulation in acute respiratory failure, such as that observed in severe COVID-19 patients, by inhibiting complement activation through exosomal CD59, thereby disrupting the feed-forward loop between complements and neutrophils to inhibit the amplification and perpetuation of inflammation during SARS-CoV-2 infection.
URI: https://hdl.handle.net/10356/162798
ISSN: 1465-3249
DOI: 10.1016/j.jcyt.2021.12.003
Schools: School of Biological Sciences 
Organisations: Singapore Immunology Network, A*STAR
Yong Loo Lin School of Medicine, NUS
Rights: © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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