ArticleThe Journal of clinical investigation2015
Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01862068 (Neutrophils Function and Identification of Prognostic Factors in Granulomatosis With Polyangiitis), which is not on this map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neutrophils Function and Identification of Prognostic Factors in Granulomatosis With Polyangiitis (Formerly Named Wegener's Granulomatosis).
Who cites it
48 citing papers in PubMed, 102 citations in OpenAlex.
- Cathepsin C-driven enhancement of neutrophil extracellular trap formation contributes to acute lung injury.iScience · 2025Article
- Proteinase 3 is involved in presepsin production through neutrophil extracellular trap phagocytosis by macrophages.Scientific reports · 2025Article
- Dendritic cell heterogeneity and its role in connective tissue diseases.Inflammation and regeneration · 2025Review
- Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis.Journal of advanced research · 2025Review
- Granulomatosis with polyangiitis presenting with isolated external genital and urethral manifestations: a case-based review.Rheumatology international · 2025Review
- Immune cell crosstalk between ANCA-associated vasculitis and IgG4-related disease: an unresolved pathogenic link.Frontiers in immunology · 2025Review
- Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome.International journal of molecular sciences · 2024Review
- Efferocytosis: Current status and future prospects in the treatment of autoimmune diseases.Heliyon · 2024Review
- The intricate relationship between autoimmunity disease and neutrophils death patterns: a love-hate story.Apoptosis : an international journal on programmed cell death · 2023Review
- Current perspective on biological properties of plasmacytoid dendritic cells and dysfunction in gut.Immunity, inflammation and disease · 2023Review
- Proteinase 3 promotes formation of multinucleated giant cells and granuloma-like structures in patients with granulomatosis with polyangiitis.Annals of the rheumatic diseases · 2023Article
- An overlap of IgG4-related tubulointerstitial nephritis and microscopic polyangiitis-associated glomerulonephritis: a case-based review.Clinical rheumatology · 2023Review
- Toll-like Receptor 9 Induced Dendritic Cell Activation Promotes Anti-Myeloperoxidase Autoimmunity and Glomerulonephritis.International journal of molecular sciences · 2023Article
- Associations of the circulating levels of cytokines with risk of ankylosing spondylitis: a Mendelian randomization study.Frontiers in immunology · 2023Article
- Protective α1-antitrypsin effects in autoimmune vasculitis are compromised by methionine oxidation.The Journal of clinical investigation · 2022Article
- [Granulomatous vasculitides and vasculitides with extravascular granulomatosis].Zeitschrift fur Rheumatologie · 2022Review
- Roles of neutrophil granule proteins in orchestrating inflammation and immunity.The FEBS journal · 2022Review
- Immunogenic cell death as driver of autoimmunity in granulomatosis with polyangiitis.Frontiers in immunology · 2022Review
- The Immunogenetics of Vasculitis.Advances in experimental medicine and biology · 2022Review
- Dynamic Changes in the Nasal Microbiome Associated With Disease Activity in Patients With Granulomatosis With Polyangiitis.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88 signaling pathway and was dependent on the synthesis of NO, as macrophages from animals lacking these pathways did not exhibit a PR3-associated proinflammatory response. The PR3-induced microenvironment facilitated recruitment of inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and neutrophils, which were observed in close proximity within granulomatous lesions in the lungs of GPA patients. In different murine models of apoptotic cell injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization. Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts immune silencing associated with clearance of apoptotic neutrophils and provide insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.