ArticleeLife2024
Uremic toxin indoxyl sulfate induces trained immunity via the AhR-dependent arachidonic acid pathway in end-stage renal disease (ESRD).
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Recipient-driven and donor-driven determinants of delayed graft function in paired kidney transplantation: evidence from a Chinese cohort.Renal failure · 2026Article
- Trained Immunity as a Mechanistic Bridge Between Uremic Toxins, Atherosclerosis, and Vascular Calcification in Chronic Kidney Disease.Cardiovascular toxicology · 2026Review
- Trained Immunity as a Mechanistic Bridge Between Uremic Toxins, Atherosclerosis, and Vascular Calcification in Chronic Kidney Disease.Cardiovascular toxicology · 2026Review
- Innate Immune Memory Responses in Organ Transplantation.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Trained immunity: An unexplored component of IBD pathogenesis.Inflammatory bowel diseases · 2026Review
- Immunosenescence in systemic and multi-organ aging: mechanisms, inter-organ crosstalk, and translational opportunities.npj aging · 2026Review
- Trained immunity modulators: A new frontier in immunoregulation and disease intervention.Journal of advanced research · 2026Review
- Microbiota-Derived Metabolites in Developmental Programming: Bridging Early-Life Gut Microbiota to Childhood Metabolic Disorders.Current medical science · 2026Review
- The Gut-Kidney-Metabolic Axis: Impact of Gut-Derived Uremic Toxins on Insulin Resistance in Diabetic Kidney Disease.International journal of molecular sciences · 2026Review
- Chronic Kidney Disease-Associated Defect in Humoral Immune Response Is Driven by Inflammation.Toxins · 2026Article
- Lactobacillus acidophilus KBL409 improves serum indoxyl sulfate via gut microbial changes in a human study.NPJ science of food · 2026Article
- Review
- Clarifying Molecular Mechanisms and Novel Strategies for Intervention of Uremia and Cognitive Decline.Kidney & blood pressure research · 2026Review
- Gut-kidney axis in IgA nephropathy: mechanisms linking microbiota dysbiosis to immune dysregulation, Gd-IgA1 generation, and renal injury.Frontiers in immunology · 2026Review
- Trained Immunity and Cardiovascular Risk: An Immunological Perspective.Immunological reviews · 2026Review
- Immune profiling in a living human recipient of a gene-edited pig kidney.Nature medicine · 2026Article
- Microbiota-driven epigenetic programming of local immunity.Frontiers in immunology · 2026Review
- Cognitive impairment in chronic kidney disease: mechanisms, clinical manifestations, and management strategies.Metabolic brain disease · 2025Review
- Deciphering the antiviral mechanisms of Fangqin Qinggan decoction against influenza A virus: a multi-omics and machine learning approach.Chinese medicine · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Trained immunity is the long-term functional reprogramming of innate immune cells, which results in altered responses toward a secondary challenge. Despite indoxyl sulfate (IS) being a potent stimulus associated with chronic kidney disease (CKD)-related inflammation, its impact on trained immunity has not been explored. Here, we demonstrate that IS induces trained immunity in monocytes via epigenetic and metabolic reprogramming, resulting in augmented cytokine production. Mechanistically, the aryl hydrocarbon receptor (AhR) contributes to IS-trained immunity by enhancing the expression of arachidonic acid (AA) metabolism-related genes such as arachidonate 5-lipoxygenase (ALOX5) and ALOX5 activating protein (ALOX5AP). Inhibition of AhR during IS training suppresses the induction of IS-trained immunity. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and after 6 days training, they exhibit enhanced TNF-α and IL-6 production to lipopolysaccharide (LPS). Furthermore, healthy control-derived monocytes trained with uremic sera from ESRD patients exhibit increased production of TNF-α and IL-6. Consistently, IS-trained mice and their splenic myeloid cells had increased production of TNF-α after in vivo and ex vivo LPS stimulation compared to that of control mice. These results provide insight into the role of IS in the induction of trained immunity, which is critical during inflammatory immune responses in CKD patients.
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Registered trials
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