ArticleClinical & translational immunology2021
Blunted sFasL signalling exacerbates TNF-driven neutrophil necroptosis in critically ill COVID-19 patients.
Article in Clinical & translational immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Pilot longitudinal integrated transcriptomic-metabolomic study reveals immune and metabolic signatures in non-hospitalized healthcare workers with long COVID.Frontiers in cellular and infection microbiology · 2026Article
- Coronavirus endoribonuclease antagonizes ZBP1-mediated necroptosis and delays multiple cell death pathways.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Clara cell 16 kDa protein: an important marker for COVID-19 severity.Frontiers in immunology · 2025Article
- Safety and efficacy of selective RIPK1 inhibitor SIR1-365 in hospitalized patients with severe COVID-19: A multicenter, randomized, double-blind, phase 1b trial.Journal of intensive medicine · 2025Article
- RIPK1 signaling pathways: implications for autoimmune and neuroinflammatory diseases.Frontiers in immunology · 2025Review
- Survivin: A key apoptosis inhibitor in COVID-19 infection and its implication for treatment protocol.Saudi journal of biological sciences · 2024Article
- Article
- Extensive acute and sustained changes to neutrophil proteomes post-SARS-CoV-2 infection.The European respiratory journal · 2024Observational
- Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo.Cell death & disease · 2024Article
- CCR5/CXCR3 antagonist TAK-779 prevents diffuse alveolar damage of the lung in the murine model of the acute respiratory distress syndrome.Frontiers in pharmacology · 2024Article
- Differential activation of programmed cell death in patients with severe SARS-CoV-2 infection.Cell death discovery · 2023Article
- Targeting Neutrophil βBiomolecules · 2023Review
- Differentially Expressed Inflammatory Cell Death-Related Genes and the Serum Levels of IL-6 are Determinants for Severity of Coronaviruses Diseases-2019 (COVID-19).Advanced biomedical research · 2023Article
- Plasma Levels of sFas-sFasL andBiomolecules · 2022Article
- RIP kinases and necroptosis in aging and aging-related diseases.Life medicine · 2022Review
- Review
- Programmed cell death: the pathways to severe COVID-19?The Biochemical journal · 2022Review
- Hyperinflammatory environment drives dysfunctional myeloid cell effector response to bacterial challenge in COVID-19.PLoS pathogens · 2022Article
- Serum soluble Fas ligand is a severity and mortality prognostic marker for COVID-19 patients.Frontiers in immunology · 2022Article
- Intervertebral disc cell chondroptosis elicits neutrophil response inFrontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesCritically ill coronavirus disease 2019 (COVID-19) patients are characterised by a severely dysregulated cytokine profile and elevated neutrophil counts, impacting disease severity. However, it remains unclear how neutrophils contribute to pathophysiology during COVID-19. Here, we assessed the impact of the dysregulated cytokine profile on the regulated cell death (RCD) programme of neutrophils.
methodsRegulated cell death phenotype of neutrophils isolated from critically ill COVID-19 patients or healthy donors and stimulated with COVID-19 or healthy plasma
resultsCOVID-19 plasma induced a necroptosis-sensitive neutrophil phenotype, characterised by cell lysis, elevated release of damage-associated molecular patterns (DAMPs), increased receptor-interacting serine/threonine-protein kinase (RIPK) 1 levels and mixed lineage kinase domain-like pseudokinase (MLKL) involvement. The occurrence of neutrophil necroptosis MLKL axis was further confirmed in COVID-19 thrombus and lung biopsies. Necroptosis was induced by the tumor necrosis factor receptor 1 (TNFRI)/TNF-α axis. Moreover, reduction of soluble Fas ligand (sFasL) levels in COVID-19 patients and hence decreased signalling to Fas directly increased RIPK1 levels, exacerbated TNF-driven necroptosis and correlated with disease severity, which was abolished in patients treated with glucocorticoids.
conclusionOur results suggest a novel role for sFasL signalling in the TNF-α-induced RCD programme in neutrophils during COVID-19 and a potential therapeutic target to curb inflammation and thus influence disease severity and outcome.
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