ArticleAnnals of the rheumatic diseases2019
REDD1/autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE) through NETs decorated with tissue factor (TF) and interleukin-17A (IL-17A).
Article in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
161 citing papers in PubMed, 2 syntheses or guidelines pooled it, 252 citations in OpenAlex.
- Trends and collaborations in discoid lupus erythematosus research: a bibliometric analysis from 2010 to 2024.Frontiers in medicine · 2025Pooled it
- Diverse Roles of NETosis in the Pathogenesis of Lupus.Frontiers in immunology · 2022Pooled it
- Myocardial injury in systemic lupus erythematosus and lupus nephritis: a silent threat.Clinical kidney journal · 2026Review
- Disease modification in lupus nephritis: towards a pathophysiology-based treatment paradigm.Nature reviews. Nephrology · 2026Review
- Inhibition of STING modulates dendritic cell responses and ameliorates podocyte injury in SLE.Lupus science & medicine · 2026Article
- NLRX1 is a critical neutrophil checkpoint modulating ferroptosis and suppressing NETosis to attenuate joint damage in arthritis.Cell death and differentiation · 2026Article
- Spatial proteomics reveals four-stage molecular evolution in cancer immunotherapy-related gastritis.Molecular cancer · 2026Article
- A neutrophil-mesangial cell axis promotes glomerular injury in lupus nephritis.Annals of the rheumatic diseases · 2026Article
- Hippocampal REDD1 inhibition is critical for alleviating depressive-like behaviors.Acta pharmacologica Sinica · 2026Article
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- Neutrophil extracellular traps in post-traumatic urethral microenvironment promote hypertrophic urethral stricture via the TLR9/NF-kB/Smad3/IL-8 axis.Apoptosis : an international journal on programmed cell death · 2026Article
- Peripheral blood transcriptomic analysis of patients with rheumatoid arthritis associated interstitial lung disease reveals: distinct molecular signature with evidence of humoral and myeloid immunity.Arthritis research & therapy · 2026Article
- Histidine alleviates Hashimoto's thyroiditis via the neutrophil extracellular traps-NF-κB signaling pathway.Scientific reports · 2026Article
- Review
- TREM2 Drives Neutrophil Extracellular Traps-Induced Dendritic Cell Maturation and Contributes to Lupus Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanistic and functional characterization of NETs/IL-17 as a therapeutic target in EMT and brain metastasis of lung adenocarcinoma.Frontiers in immunology · 2026Article
- Inhibition of neutrophil infiltration and NETs formation ameliorates neuropsychiatric and renal dysfunction in MRL/lpr mice with lupus.PloS one · 2026Article
- Article
- Neutrophil extracellular traps in asthma and chronic obstructive pulmonary disease: pathogenic roles, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Neutrophil Extracellular Traps in Systemic Lupus Erythematosus: Pathogenic Mechanisms, Crosstalk with Oxidative Stress, and Antioxidant Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2025Review
101 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThe release of neutrophil extracellular traps (NETs) represents a novel neutrophil effector function in systemic lupus erythematosus (SLE) pathogenesis. However, the molecular mechanism underlying NET release and how NETs mediate end-organ injury in SLE remain elusive.
methodsNET formation and NET-related proteins were assessed in the peripheral blood and biopsies from discoid lupus and proliferative nephritis, using immunofluorescence, immunoblotting, quantitative PCR and ELISA. Autophagy was assessed by immunofluorescence and immunoblotting. The functional effects of NETs in vitro were assessed in a primary fibroblast culture.
resultsNeutrophils from patients with active SLE exhibited increased basal autophagy levels leading to enhanced NET release, which was inhibited in vitro by hydroxychloroquine. NETosis in SLE neutrophils correlated with increased expression of the stress-response protein REDD1. Endothelin-1 (ET-1) and hypoxia-inducible factor-1α (HIF-1α) were key mediators of REDD1-driven NETs as demonstrated by their inhibition with bosentan and L-ascorbic acid, respectively. SLE NETs were decorated with tissue factor (TF) and interleukin-17A (IL-17A), which promoted thrombin generation and the fibrotic potential of cultured skin fibroblasts. Notably, TF-bearing and IL-17A-bearing NETs were abundant in discoid skin lesions and in the glomerular and tubulointerstitial compartment of proliferative nephritis biopsy specimens.
conclusionsOur data suggest the involvement of REDD1/autophagy/NET axis in end-organ injury and fibrosis in SLE, a likely candidate for repositioning of existing drugs for SLE therapy. Autophagy-mediated release of TF-bearing and IL-17A-bearing NETs provides a link between thromboinflammation and fibrosis in SLE and may account for the salutary effects of hydroxychloroquine.
Indexed as
Identifiers
What OpenQuestion holds
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.