ArticleAnnals of the rheumatic diseases2018
Differential ubiquitination in NETs regulates macrophage responses in systemic lupus erythematosus.
Article in Annals of the rheumatic diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Diverse Roles of NETosis in the Pathogenesis of Lupus.Frontiers in immunology · 2022Pooled it
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- A neutrophil-mesangial cell axis promotes glomerular injury in lupus nephritis.Annals of the rheumatic diseases · 2026Article
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Immunopathogenesis of accelerated atherosclerosis in systemic lupus erythematosus: from innate and adaptive dysregulation to clinical implications.Frontiers in immunology · 2026Review
- Advances in the study of low-density neutrophils in rheumatic diseases.Frontiers in immunology · 2026Review
- A comprehensive insight into NETosis-extracellular vesicle crosstalk in autoimmune diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Biological roles and clinical translation of low-density neutrophils in rheumatic, autoimmune and inflammatory diseases: paradigm reconstruction and unresolved questions.Frontiers in immunology · 2026Review
- Antibody-opsonized extracellular traps modulate macrophage responses and attenuate their T cell-associated inflammatory and costimulatory characteristics.Frontiers in immunology · 2026Article
- Neutrophils and NETs in Pathophysiology and Treatment of Inflammatory Bowel Disease.International journal of molecular sciences · 2025Review
- Interaction of low-density neutrophils with other immune cells in the mechanism of inflammation.Molecular medicine (Cambridge, Mass.) · 2025Review
- Neutrophil extracellular traps induce intrahepatic thrombotic tendency and liver damage in cholestatic liver disease.Hepatology communications · 2024Article
- Almost 50 Years of Monomeric Extracellular Ubiquitin (eUb).Pharmaceuticals (Basel, Switzerland) · 2024Review
- CAR T-cell therapy for systemic lupus erythematosus: current status and future perspectives.Frontiers in immunology · 2024Review
- Exploring the ROS reduction strategies in chronic lupus management.Frontiers in immunology · 2024Article
- Review
- Low-density granulocytes in systemic autoimmunity and autoinflammation.Immunological reviews · 2023Review
- Roles of macrophages on ulcerative colitis and colitis-associated colorectal cancer.Frontiers in immunology · 2023Review
- Proteomics analysis of lysine crotonylation and 2-hydroxyisobutyrylation reveals significant features of systemic lupus erythematosus.Clinical rheumatology · 2022Article
- Serum extracellular traps associate with the activation of myeloid cells in SLE patients with the low level of anti-DNA antibodies.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesTo assess if ubiquitinated proteins potentially present in neutrophil extracellular traps (NETs) can modify cellular responses and induce inflammatory mechanisms in patients with systemic lupus erythematosus (SLE) and healthy subjects. MATERIALS AND
methodsWe studied 74 subjects with SLE and 77 healthy controls. Neutrophils and low-density granulocytes were isolated, and NETs were induced. Ubiquitin content was quantified in NETs by western blot analysis, ELISA and immunofluorescence microscopy, while ubiquitination of NET proteins was assessed by immunoprecipitation. Monocyte-derived macrophages from SLE and controls were isolated and stimulated with NETs or ubiquitin. Calcium flux and cytokine synthesis were measured following these stimuli.
resultsNETs contain ubiquitinated proteins, with a lower expression of polyubiquitinated proteins in subjects with SLE than in controls. Myeloperoxidase (MPO) is present in ubiquitinated form in NETs. Patients with SLE develop antiubiquitinated MPO antibodies, and titres positively correlate with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (P<0.01), and negatively correlate with complement components (P<0.01). Stimulation of monocyte-derived macrophages with NETs or with ubiquitin led to enhanced calcium flux. In addition, stimulation with NETs led to enhanced cytokine (tumour necrosis factor-α and interleukin-10) production in macrophages from patients with SLE when compared with controls, which was hampered by inhibition of NET internalisation by macrophages.
conclusionThis is the first study to find ubiquitinated proteins in NETs, and evidence for adaptive immune responses directed towards ubiquitinated NET proteins in SLE. The distinct differences in ubiquitin species profile in NETs compared with healthy controls may contribute to dampened anti-inflammatory responses observed in SLE. These results also support a role for extracellular ubiquitin in inflammation in SLE.
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