Inhibition of SARS‐CoV‐2‐mediated thromboinflammation by CLEC2.Fc
Abstract Thromboinflammation is the major cause of morbidity and mortality in COVID‐19 patients, and post‐mortem examination demonstrates the presence of platelet‐rich thrombi and microangiopathy in visceral organs. Moreover, persistent microclots were detected in both acute COVID‐19 and long COVID...
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-05-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202216351 |
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| author | Pei‐Shan Sung Cheng‐Pu Sun Mi‐Hua Tao Shie‐Liang Hsieh |
| author_facet | Pei‐Shan Sung Cheng‐Pu Sun Mi‐Hua Tao Shie‐Liang Hsieh |
| author_sort | Pei‐Shan Sung |
| collection | DOAJ |
| description | Abstract Thromboinflammation is the major cause of morbidity and mortality in COVID‐19 patients, and post‐mortem examination demonstrates the presence of platelet‐rich thrombi and microangiopathy in visceral organs. Moreover, persistent microclots were detected in both acute COVID‐19 and long COVID plasma samples. However, the molecular mechanism of SARS‐CoV‐2‐induced thromboinflammation is still unclear. We found that the spleen tyrosine kinase (Syk)‐coupled C‐type lectin member 2 (CLEC2), which was highly expressed in platelets and alveolar macrophages, interacted with the receptor‐binding domain (RBD) of SARS‐CoV‐2 spike protein (SARS‐CoV‐2 RBD) directly. Unlike the thread‐like NETs, SARS‐CoV‐2‐induced aggregated NET formation in the presence of wild‐type (WT), but not CLEC2‐deficient platelets. Furthermore, SARS‐CoV‐2 spike pseudotyped lentivirus was able to induce NET formation via CLEC2, indicating SARS‐CoV‐2 RBD engaged CLEC2 to activate platelets to enhance NET formation. Administration of CLEC2.Fc inhibited SARS‐CoV‐2‐induced NET formation and thromboinflammation in AAV‐ACE2‐infected mice. Thus, CLEC2 is a novel pattern recognition receptor for SARS‐CoV‐2, and CLEC2.Fc and may become a promising therapeutic agent to inhibit SARS‐CoV‐2‐induced thromboinflammation and reduced the risk of post‐acute sequelae of COVID‐19 (PASC) in the future. |
| first_indexed | 2024-03-13T00:33:39Z |
| format | Article |
| id | doaj.art-3904477d13b745f885c6bee143b14514 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T08:24:26Z |
| publishDate | 2023-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-3904477d13b745f885c6bee143b145142024-11-03T12:37:59ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-05-0115711610.15252/emmm.202216351Inhibition of SARS‐CoV‐2‐mediated thromboinflammation by CLEC2.FcPei‐Shan Sung0Cheng‐Pu Sun1Mi‐Hua Tao2Shie‐Liang Hsieh3Genomics Research Center, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaGenomics Research Center, Academia SinicaAbstract Thromboinflammation is the major cause of morbidity and mortality in COVID‐19 patients, and post‐mortem examination demonstrates the presence of platelet‐rich thrombi and microangiopathy in visceral organs. Moreover, persistent microclots were detected in both acute COVID‐19 and long COVID plasma samples. However, the molecular mechanism of SARS‐CoV‐2‐induced thromboinflammation is still unclear. We found that the spleen tyrosine kinase (Syk)‐coupled C‐type lectin member 2 (CLEC2), which was highly expressed in platelets and alveolar macrophages, interacted with the receptor‐binding domain (RBD) of SARS‐CoV‐2 spike protein (SARS‐CoV‐2 RBD) directly. Unlike the thread‐like NETs, SARS‐CoV‐2‐induced aggregated NET formation in the presence of wild‐type (WT), but not CLEC2‐deficient platelets. Furthermore, SARS‐CoV‐2 spike pseudotyped lentivirus was able to induce NET formation via CLEC2, indicating SARS‐CoV‐2 RBD engaged CLEC2 to activate platelets to enhance NET formation. Administration of CLEC2.Fc inhibited SARS‐CoV‐2‐induced NET formation and thromboinflammation in AAV‐ACE2‐infected mice. Thus, CLEC2 is a novel pattern recognition receptor for SARS‐CoV‐2, and CLEC2.Fc and may become a promising therapeutic agent to inhibit SARS‐CoV‐2‐induced thromboinflammation and reduced the risk of post‐acute sequelae of COVID‐19 (PASC) in the future.https://doi.org/10.15252/emmm.202216351CLEC2NETplateletSARS‐CoV‐2thromboinflammation |
| spellingShingle | Pei‐Shan Sung Cheng‐Pu Sun Mi‐Hua Tao Shie‐Liang Hsieh Inhibition of SARS‐CoV‐2‐mediated thromboinflammation by CLEC2.Fc EMBO Molecular Medicine CLEC2 NET platelet SARS‐CoV‐2 thromboinflammation |
| title | Inhibition of SARS‐CoV‐2‐mediated thromboinflammation by CLEC2.Fc |
| title_full | Inhibition of SARS‐CoV‐2‐mediated thromboinflammation by CLEC2.Fc |
| title_fullStr | Inhibition of SARS‐CoV‐2‐mediated thromboinflammation by CLEC2.Fc |
| title_full_unstemmed | Inhibition of SARS‐CoV‐2‐mediated thromboinflammation by CLEC2.Fc |
| title_short | Inhibition of SARS‐CoV‐2‐mediated thromboinflammation by CLEC2.Fc |
| title_sort | inhibition of sars cov 2 mediated thromboinflammation by clec2 fc |
| topic | CLEC2 NET platelet SARS‐CoV‐2 thromboinflammation |
| url | https://doi.org/10.15252/emmm.202216351 |
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