ArticleJournal of the American Society of Nephrology : JASN2012
Uromodulin triggers IL-1β-dependent innate immunity via the NLRP3 inflammasome.
Article in Journal of the American Society of Nephrology : JASN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 127 citations in OpenAlex.
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Uromodulin p.His36Tyr promotes macrophage pyroptosis via App-Cd74 signaling to drive renal inflammation in ADTKD.Nature communications · 2026Article
- Recent advances in the clinical significance and physiological functions of uromodulin: a narrative review.BMC nephrology · 2026Review
- Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026Review
- A salty symphony: unraveling the tale of uromodulin and sodium sensitivity.Journal of human hypertension · 2025Review
- Serum Uromodulin as early marker for ischemic acute kidney injury and nephron loss: association with kidney tissue distribution pattern.Journal of translational medicine · 2025Article
- Advances in uromodulin biology and potential clinical applications.Nature reviews. Nephrology · 2024Review
- Relationship Between Serum Uromodulin as a Marker of Kidney Damage and Metabolic Status in Patients with Chronic Kidney Disease of Non-Diabetic Etiology.International journal of molecular sciences · 2024Article
- Uromodulin biology.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Cilostazol protects against degenerative cervical myelopathy injury and cell pyroptosis via TXNIP-NLRP3 pathway.Cell division · 2024Article
- New insights into the role of immunity and inflammation in diabetic kidney disease in the omics era.Frontiers in immunology · 2024Review
- Association of serum copeptin and urinary uromodulin with kidney function, blood pressure and albuminuria at 6 weeks post-partum in pre-eclampsia.Frontiers in cardiovascular medicine · 2024Article
- Oxalate‑induced renal pyroptotic injury and crystal formation mediated by NLRP3‑GSDMD signalingMolecular medicine reports · 2023Article
- Emerging evidence on the role of clonal hematopoiesis of indeterminate potential in chronic kidney disease.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Association betweenInternational journal of molecular sciences · 2023Article
- NETosis: an emerging therapeutic target in renal diseases.Frontiers in immunology · 2023Review
- Diverse Pathways of Engineered Nanoparticle-Induced NLRP3 Inflammasome Activation.Nanomaterials (Basel, Switzerland) · 2022Review
- Novel insights into NOD-like receptors in renal diseases.Acta pharmacologica Sinica · 2022Review
- Identification and characterization of murine glycoprotein 2-expressing intestinal dendritic cells.Scandinavian journal of immunology · 2022Article
- Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uromodulin/Tamm-Horsfall protein is not immunostimulatory in the tubular lumen, but through unknown mechanisms it can activate dendritic cells and promote inflammation in the renal interstitium. Here, we noted that uromodulin isolated from human urine aggregates to large, irregular clumps with a crystal-like ultrastructure. These uromodulin nanoparticles activated isolated human monocytes to express costimulatory molecules and to secrete the mature proinflammatory cytokines, including IL-1β. Full release of IL-1β in response to uromodulin depended on priming of pro-IL-1β expression by Toll-like receptors, TNF-α, or IL-1α. In addition, uromodulin-induced secretion of mature IL-1β depended on the NLRP3 inflammasome, its linker molecule ASC, and pro-IL-1β cleavage by caspase-1. Activation of NLRP3 required phagocytosis of uromodulin particles into lysosomes, cathepsin leakage, oxidative stress, and potassium efflux from the cell. Taken together, these data suggest that uromodulin is a NLRP3 agonist handled by antigen-presenting cells as an immunostimulatory nanoparticle. Thus, in the presence of tubular damage that exposes the renal interstitium, uromodulin becomes an endogenous danger signal. The inability of renal parenchymal cells to secrete IL-1β may explain why uromodulin remains immunologically inert inside the luminal compartment of the urinary tract.
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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.