ArticleNature2014
Aryl hydrocarbon receptor control of a disease tolerance defence pathway.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 430 papers.
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
430 citing papers in PubMed, 665 citations in OpenAlex.
- Reshaping the tumor microenvironment of cold soft-tissue sarcomas with anti-angiogenics: a phase 2 trial of regorafenib combined with avelumab.Signal transduction and targeted therapy · 2025Trial
- Efficacy of a postbiotic and its components in promoting colonic transit and alleviating chronic constipation in humans and mice.Cell reports. Medicine · 2025Trial
- Regorafenib plus avelumab in advanced gastroenteropancreatic neuroendocrine neoplasms: a phase 2 trial and correlative analysis.Nature cancer · 2025Trial
- Dietary tryptophan mitigates lung ischemia-reperfusion injury in association with increased indole-3-propionate and aryl hydrocarbon receptor signaling.Gut microbes · 2026Article
- Pseudomonas aeruginosa-derived volatile organic compounds modulate AhR signaling to dysregulate airway mucus homeostasis.Nature communications · 2026Article
- Mechanism-First Psychobiotics: Fermented Vegetables, Dairy, and Soy for Depression and Anxiety.International journal of molecular sciences · 2026Review
- AhR as a Common Denominator in Immunity and Inflammation in Chronic Lung Diseases: Molecular and Clinical Insights.Diseases (Basel, Switzerland) · 2026Review
- Metabolic pattern changes of macrophages during cancer development and progression.Journal of translational medicine · 2026Review
- Cell Signaling by Tryptophan Catabolism.Biochemistry · 2026Review
- Review
- Monocytes from inflammatory arthritis patients accumulate methotrexate and their transcriptome predicts methotrexate clinical response.Cellular and molecular life sciences : CMLS · 2026Article
- Identification of alterations of immunometabolism associated with Pompe disease.Cellular and molecular life sciences : CMLS · 2026Article
- Multiomics Analyses Reveal an Essential Role of Tryptophan in Treatment of csDMARDs in Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Aryl hydrocarbon receptor regulates programmed cell death in diseases: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- The kynurenine pathway in RNA virus infection: immunometabolic control of antiviral defense and viral persistence.Frontiers in immunology · 2026Review
- Tanshinone IIA restores CD8Frontiers in pharmacology · 2026Article
- Gut Metabolite Indoleacrylic Acid Suppresses Osteoclast Formation by AHR mediated NF-κB Signaling Pathway.International journal of biological sciences · 2026Article
- Gut microbiota-regulated tryptophan metabolism in breast cancer: mechanisms and therapeutic perspectives.Frontiers in oncology · 2026Review
- T cell exhaustion landscapes and therapeutic modulation in cancer immunity.Frontiers in cell and developmental biology · 2026Review
- Friend or foe: the gut microbiota as a modulator of disease trajectory in trauma, surgery, and critical illness.Gut microbes · 2025Review
370 more citing papers are in PubMed but not listed here.
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Authors and funding
38 authors at 15 institutions in 8 countries.
Funding
Abstract
Disease tolerance is the ability of the host to reduce the effect of infection on host fitness. Analysis of disease tolerance pathways could provide new approaches for treating infections and other inflammatory diseases. Typically, an initial exposure to bacterial lipopolysaccharide (LPS) induces a state of refractoriness to further LPS challenge (endotoxin tolerance). We found that a first exposure of mice to LPS activated the ligand-operated transcription factor aryl hydrocarbon receptor (AhR) and the hepatic enzyme tryptophan 2,3-dioxygenase, which provided an activating ligand to the former, to downregulate early inflammatory gene expression. However, on LPS rechallenge, AhR engaged in long-term regulation of systemic inflammation only in the presence of indoleamine 2,3-dioxygenase 1 (IDO1). AhR-complex-associated Src kinase activity promoted IDO1 phosphorylation and signalling ability. The resulting endotoxin-tolerant state was found to protect mice against immunopathology in Gram-negative and Gram-positive infections, pointing to a role for AhR in contributing to host fitness.
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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.