ArticleRheumatology (Oxford, England)2024
Platelet TLR7 is essential for the formation of platelet-neutrophil complexes and low-density neutrophils in lupus nephritis.
Article in Rheumatology (Oxford, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- Low-Density Granulocytes Link to Disease Activity, Organ Involvement, and Cytokine Production in Sjögren's Disease.International journal of molecular sciences · 2026Article
- Neutrophils as critical orchestrators of chronic inflammation.Cellular & molecular immunology · 2026Review
- Can Phagocytosis, Neutrophil Extracellular Traps, and IFN-α Production in Systemic Lupus Erythematosus Be Simultaneously Modulated? A Pharmacological Perspective.International journal of molecular sciences · 2026Review
- Platelets in systemic lupus erythematosus: from hemostatic allies to pathogenic drivers.Frontiers in immunology · 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
- Advances in the study of low-density neutrophils in rheumatic diseases.Frontiers in immunology · 2026Review
- Recent insights into the role of innate immunity in lupus.Human molecular genetics · 2025Review
- Platelets as drivers of immunothrombosis in rheumatic diseases.Nature reviews. Rheumatology · 2025Review
- Neutrophils and Platelets as Key Players in the Pathogenesis of ANCA-Associated Vasculitis and Potential Sources of Disease Activity Biomarkers.Diagnostics (Basel, Switzerland) · 2025Review
- Platelets and diseases: signal transduction and advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Interaction of low-density neutrophils with other immune cells in the mechanism of inflammation.Molecular medicine (Cambridge, Mass.) · 2025Review
- Platelet signaling in immune landscape: comprehensive mechanism and clinical therapy.Biomarker research · 2024Review
- Maturing neutrophils of lower density associate with thrombocytopenia in Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome.Frontiers in immunology · 2024Article
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Authors and funding
25 authors at 9 institutions in 4 countries.
Funding
Abstract
objectivesPlatelets and low-density neutrophils (LDNs) are major players in the immunopathogenesis of SLE. Despite evidence showing the importance of platelet-neutrophil complexes (PNCs) in inflammation, little is known about the relationship between LDNs and platelets in SLE. We sought to characterize the role of LDNs and Toll-like receptor 7 (TLR7) in clinical disease.
methodsFlow cytometry was used to immunophenotype LDNs from SLE patients and controls. The association of LDNs with organ damage was investigated in a cohort of 290 SLE patients. TLR7 mRNA expression was assessed in LDNs and high-density neutrophils (HDNs) using publicly available mRNA sequencing datasets and our own cohort using RT-PCR. The role of TLR7 in platelet binding was evaluated in platelet-HDN mixing studies using TLR7-deficient mice and Klinefelter syndrome patients.
resultsSLE patients with active disease have more LDNs, which are heterogeneous and more immature in patients with evidence of kidney dysfunction. LDNs are platelet bound, in contrast to HDNs. LDNs settle in the peripheral blood mononuclear cell (PBMC) layer due to the increased buoyancy and neutrophil degranulation from platelet binding. Mixing studies demonstrated that this PNC formation was dependent on platelet-TLR7 and that the association results in increased NETosis. The neutrophil:platelet ratio is a useful clinical correlate for LDNs, and a higher NPR is associated with past and current flares of LN.
conclusionsLDNs sediment in the upper PBMC fraction due to PNC formation, which is dependent on the expression of TLR7 in platelets. Collectively, our results reveal a novel TLR7-dependent crosstalk between platelets and neutrophils that may be an important therapeutic opportunity for LN.
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