ArticleKidney international2020
TLR9 activation induces aberrant IgA glycosylation via APRIL- and IL-6-mediated pathways in IgA nephropathy.
Article in Kidney international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 3 of them syntheses that pooled it.
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Who cites it
100 citing papers in PubMed, 3 syntheses or guidelines pooled it, 154 citations in OpenAlex.
- Efficacy and safety of sibeprenlimab in IgA nephropathy: a systematic review and meta-analysis of randomized controlled trials.BMC nephrology · 2026Pooled it
- Role of hydroxychloroquine in primary glomerular disease - a systematic review and meta-analysis of the current evidence.BMC nephrology · 2025Pooled it
- Hydroxychloroquine in IgA nephropathy: a systematic review.Renal failure · 2021Pooled it
- A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy.The New England journal of medicine · 2024Trial
- Infectious triggers in IgA vasculitis in children: current evidence, causal attribution and immunopathogenic mechanisms.Rheumatology international · 2026Review
- Bronchial lesions in a high serum IgA mouse model: pulmonary venular IgA deposition and spatially distinct lymphoid cell aggregation.Journal of pathology and translational medicine · 2026Article
- Hydroxychloroquine use in pediatric IgA nephropathy.Pediatric nephrology (Berlin, Germany) · 2026Observational
- Renal lymphatic vessels correlate with disease activity and progression of IgA nephropathy: a retrospective cohort study.Clinical kidney journal · 2026Article
- IgA nephropathy new therapies: from data in adults to application in children.Pediatric nephrology (Berlin, Germany) · 2026Review
- Plasmacytoid dendritic cells modulate the production of mucosal IgA in IgA nephropathy.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Article
- Evaluation of immunoglobulin A1/immunoglobulin A2 ratio and B cell lymphoma-6 in relation to apoptosis-associated speck-like protein in diabetic kidney disease patients.BMC immunology · 2026Article
- Layered immune biomarker monitoring in IgA nephropathy: from mucosal IgA dysregulation to precision therapeutic response assessment.Frontiers in medicine · 2026Review
- Short interference RNAs in glomerulonephritis: A mini review.BioImpacts : BI · 2026Review
- New Insights on IgA Nephropathy from the Perspective of Active Lesions and Systemic Inflammatory Responses.ImmunoTargets and therapy · 2026Review
- The role of mucosal immune dysregulation in the pathogenesis of immunoglobulin A nephropathy.Frontiers in immunology · 2026Review
- Serum anti-β2 spectrin IgA antibodies are produced in a CD4 T cell-independent manner in IgA nephropathy model mouse.Frontiers in immunology · 2026Article
- TLR7/9-mediated mucosal innate immune dysregulation in IgA nephropathy.Frontiers in immunology · 2026Review
- Gut-kidney axis in IgA nephropathy: mechanisms linking microbiota dysbiosis to immune dysregulation, Gd-IgA1 generation, and renal injury.Frontiers in immunology · 2026Review
- Emerging Mechanistic Links Between Fucosylation and Senescence in Lung Diseases.Journal of respiratory biology and translational medicine · 2026Article
- Dioscin attenuates Gd-IgA1 overproduction by inhibiting the IL-6-JAK2/STAT3 signaling axis in IgA nephropathy.BMC nephrology · 2025Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Galactose-deficient IgA1 (Gd-IgA1) plays a crucial role in the development of IgA nephropathy (IgAN). However, the pathogenic mechanisms driving Gd-IgA1 production have not been fully elucidated. Innate-immune activation via Toll-like receptor 9 (TLR9) is known to be involved in Gd-IgA1 production. A proliferation inducing ligand (APRIL) and IL-6 are also known to enhance Gd-IgA1 synthesis in IgAN. With this as background, we investigated how TLR9 activation in IgA secreting cells results in overproduction of nephritogenic IgA in the IgAN-prone ddY mouse and in human IgA1-secreting cells. Injection of the TLR9 ligand CpG-oligonucleotides increased production of aberrantly glycosylated IgA and IgG-IgA immune complexes in ddY mice that, in turn, exacerbated kidney injury. CpG-oligonucleotide-stimulated mice had elevated serum levels of APRIL that correlated with those of aberrantly glycosylated IgA and IgG-IgA immune complexes. In vitro, TLR9 activation enhanced production of the nephritogenic IgA as well as APRIL and IL-6 in splenocytes of ddY mice and in human IgA1-secreting cells. However, siRNA knock-down of APRIL completely suppressed overproduction of Gd-IgA1 induced by IL-6. Neutralization of IL-6 decreased CpG-oligonucleotide-induced overproduction of Gd-IgA1. Furthermore, APRIL and IL-6 pathways each independently mediated TLR9-induced overproduction of Gd-IgA1. Thus, TLR9 activation enhanced synthesis of aberrantly glycosylated IgA that, in a mouse model of IgAN, further enhanced kidney injury. Hence, APRIL and IL-6 synergistically, as well as independently, enhance synthesis of Gd-IgA1.
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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.