Single-cell transcriptomic analysis reveals a systemic immune dysregulation in COVID-19-associated pediatric encephalopathy.
Wang, Y
Luu, LDW
Liu, S
Zhu, X
Huang, S
Li, F
Huang, X
Guo, L
Zhang, J
Ge, H
Sun, Y
Hui, Y
Qu, Y
Wang, H
Wang, X
Na, W
Zhou, J
Qu, D
Tai, J
- Publisher:
- SPRINGERNATURE
- Publication Type:
- Journal Article
- Citation:
- Signal Transduct Target Ther, 2023, 8, (1), pp. 398
- Issue Date:
- 2023-10-18
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Wang, Y | |
dc.contributor.author | Luu, LDW | |
dc.contributor.author | Liu, S | |
dc.contributor.author | Zhu, X | |
dc.contributor.author | Huang, S | |
dc.contributor.author | Li, F | |
dc.contributor.author | Huang, X | |
dc.contributor.author | Guo, L | |
dc.contributor.author | Zhang, J | |
dc.contributor.author | Ge, H | |
dc.contributor.author | Sun, Y | |
dc.contributor.author | Hui, Y | |
dc.contributor.author | Qu, Y | |
dc.contributor.author | Wang, H | |
dc.contributor.author | Wang, X | |
dc.contributor.author | Na, W | |
dc.contributor.author | Zhou, J | |
dc.contributor.author | Qu, D | |
dc.contributor.author | Tai, J | |
dc.date.accessioned | 2024-01-08T06:22:05Z | |
dc.date.available | 2023-09-01 | |
dc.date.available | 2024-01-08T06:22:05Z | |
dc.date.issued | 2023-10-18 | |
dc.identifier.citation | Signal Transduct Target Ther, 2023, 8, (1), pp. 398 | |
dc.identifier.issn | 2095-9907 | |
dc.identifier.issn | 2059-3635 | |
dc.identifier.uri | http://hdl.handle.net/10453/174101 | |
dc.description.abstract | Unraveling the molecular mechanisms for COVID-19-associated encephalopathy and its immunopathology is crucial for developing effective treatments. Here, we utilized single-cell transcriptomic analysis and integrated clinical observations and laboratory examination to dissect the host immune responses and reveal pathological mechanisms in COVID-19-associated pediatric encephalopathy. We found that lymphopenia was a prominent characteristic of immune perturbation in COVID-19 patients with encephalopathy, especially those with acute necrotizing encephalopathy (AE). This was characterized a marked reduction of various lymphocytes (e.g., CD8+ T and CD4+ T cells) and significant increases in other inflammatory cells (e.g., monocytes). Further analysis revealed activation of multiple cell apoptosis pathways (e.g., granzyme/perforin-, FAS- and TNF-induced apoptosis) may be responsible for lymphopenia. A systemic S100A12 upregulation, primarily from classical monocytes, may have contributed to cytokine storms in patients with AE. A dysregulated type I interferon (IFN) response was observed which may have further exacerbated the S100A12-driven inflammation in patients with AE. In COVID-19 patients with AE, myeloid cells (e.g., monocytic myeloid-derived suppressor cells) were the likely contributors to immune paralysis. Finally, the immune landscape in COVID-19 patients with encephalopathy, especially for AE, were also characterized by NK and T cells with widespread exhaustion, higher cytotoxic scores and inflammatory response as well as a dysregulated B cell-mediated humoral immune response. Taken together, this comprehensive data provides a detailed resource for elucidating immunopathogenesis and will aid development of effective COVID-19-associated pediatric encephalopathy treatments, especially for those with AE. | |
dc.format | Electronic | |
dc.language | eng | |
dc.publisher | SPRINGERNATURE | |
dc.relation.ispartof | Signal Transduct Target Ther | |
dc.relation.isbasedon | 10.1038/s41392-023-01641-y | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject.classification | 3101 Biochemistry and cell biology | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Child | |
dc.subject.mesh | CD8-Positive T-Lymphocytes | |
dc.subject.mesh | COVID-19 | |
dc.subject.mesh | S100A12 Protein | |
dc.subject.mesh | Transcriptome | |
dc.subject.mesh | CD4-Positive T-Lymphocytes | |
dc.subject.mesh | Lymphopenia | |
dc.subject.mesh | CD4-Positive T-Lymphocytes | |
dc.subject.mesh | CD8-Positive T-Lymphocytes | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Lymphopenia | |
dc.subject.mesh | Child | |
dc.subject.mesh | Transcriptome | |
dc.subject.mesh | S100A12 Protein | |
dc.subject.mesh | COVID-19 | |
dc.title | Single-cell transcriptomic analysis reveals a systemic immune dysregulation in COVID-19-associated pediatric encephalopathy. | |
dc.type | Journal Article | |
utslib.citation.volume | 8 | |
utslib.location.activity | England | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
utslib.copyright.status | open_access | * |
dc.date.updated | 2024-01-08T06:21:49Z | |
pubs.issue | 1 | |
pubs.publication-status | Published online | |
pubs.volume | 8 | |
utslib.citation.issue | 1 |
Abstract:
Unraveling the molecular mechanisms for COVID-19-associated encephalopathy and its immunopathology is crucial for developing effective treatments. Here, we utilized single-cell transcriptomic analysis and integrated clinical observations and laboratory examination to dissect the host immune responses and reveal pathological mechanisms in COVID-19-associated pediatric encephalopathy. We found that lymphopenia was a prominent characteristic of immune perturbation in COVID-19 patients with encephalopathy, especially those with acute necrotizing encephalopathy (AE). This was characterized a marked reduction of various lymphocytes (e.g., CD8+ T and CD4+ T cells) and significant increases in other inflammatory cells (e.g., monocytes). Further analysis revealed activation of multiple cell apoptosis pathways (e.g., granzyme/perforin-, FAS- and TNF-induced apoptosis) may be responsible for lymphopenia. A systemic S100A12 upregulation, primarily from classical monocytes, may have contributed to cytokine storms in patients with AE. A dysregulated type I interferon (IFN) response was observed which may have further exacerbated the S100A12-driven inflammation in patients with AE. In COVID-19 patients with AE, myeloid cells (e.g., monocytic myeloid-derived suppressor cells) were the likely contributors to immune paralysis. Finally, the immune landscape in COVID-19 patients with encephalopathy, especially for AE, were also characterized by NK and T cells with widespread exhaustion, higher cytotoxic scores and inflammatory response as well as a dysregulated B cell-mediated humoral immune response. Taken together, this comprehensive data provides a detailed resource for elucidating immunopathogenesis and will aid development of effective COVID-19-associated pediatric encephalopathy treatments, especially for those with AE.
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