ArticleJCI insight2017
Bilirubin suppresses Th17 immunity in colitis by upregulating CD39.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 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.
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Who cites it
64 citing papers in PubMed, 85 citations in OpenAlex.
- Crosstalk between the microbiota and intestinal γδ T cell compartments in health and IBD.Gut microbes · 2026Review
- Integrated metabolomics and DNA methylation signatures and their association with flare remission in SLE.Lupus science & medicine · 2026Article
- Immunomodulatory effects of tacrolimus-loaded lipid-core nanocapsules in autoimmune hepatitis.Journal of autoimmunity · 2026Article
- Esophageal epithelial cell-derived kynurenine drives Th17 inflammation in reflux esophagitis and is targeted by Xuanfu Daizhe decoction.Chinese medicine · 2026Article
- Albumin-Bilirubin Score as a Novel Prognostic Prediction Tool for Surgically Treated Head and Neck Squamous Cell Carcinoma.The Kaohsiung journal of medical sciences · 2026Article
- Inhibition of estrogen receptor alpha stabilizes regulatory T cell function in autoimmune hepatitis.JHEP reports : innovation in hepatology · 2026Article
- The HO-1/bilirubin axis in cardiovascular protection: critical evidence for modulation by plant metabolites and traditional multi-component formulations used in Chinese medicine.Frontiers in pharmacology · 2026Review
- Heme and iron toxicity in the aged spleen impairs T cell immunity through iron deprivation.Nature aging · 2025Article
- Review
- Purinergic pathways and their clinical use in the treatment of acute myeloid leukemia.Purinergic signalling · 2025Review
- Antisense to human CD39 dysregulates immune metabolism in inflammatory bowel disease.Cellular & molecular immunology · 2025Article
- Bilirubin metabolism in relation to cancer.Frontiers in oncology · 2025Review
- Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury.World journal of gastroenterology · 2024Article
- Silencing of aryl hydrocarbon receptor repressor restrains Th17 cell immunity in autoimmune hepatitis.Journal of autoimmunity · 2024Article
- Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases.Biomolecules · 2024Review
- Serum metabolites and hypercholesterolemia: insights from a two-sample Mendelian randomization study.Frontiers in cardiovascular medicine · 2024Article
- Aryl hydrocarbon receptor: current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases.Frontiers in immunology · 2024Review
- Targeted modulation of intestinal epithelial regeneration and immune response in ulcerative colitis using dual-targeting bilirubin nanoparticles.Theranostics · 2024Article
- Alterations in the intestinal microbiota associated with active tuberculosis and latent tuberculosis infection.Heliyon · 2023Article
- CD4+ T-cell subsets in autoimmune hepatitis: A review.Hepatology communications · 2023Review
4 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
14 authors at 2 institutions in 1 country.
Funding
Abstract
Unconjugated bilirubin (UCB), a product of heme oxidation, has known immunosuppressant properties but the molecular mechanisms, other than antioxidant effects, remain largely unexplored. We note that UCB modulates T helper type 17 (Th17) immune responses, in a manner dependent upon heightened expression of CD39 ectonucleotidase. UCB has protective effects in experimental colitis, where it enhances recovery after injury and preferentially boosts IL-10 production by colonic intraepithelial CD4+ cells. In vitro, UCB confers immunoregulatory properties on human control Th17 cells, as reflected by increased levels of FOXP3 and CD39 with heightened cellular suppressor ability. Upregulation of CD39 by Th17 cells is dependent upon ligation of the aryl hydrocarbon receptor (AHR) by UCB. Genetic deletion of CD39, as in Entpd1-/- mice, or dysfunction of AHR, as in Ahrd mice, abrogates these UCB salutary effects in experimental colitis. However, in inflammatory bowel disease (IBD) samples, UCB fails to confer substantive immunosuppressive properties upon Th17 cells, because of decreased AHR levels under the conditions tested in vitro. Immunosuppressive effects of UCB are mediated by AHR resulting in CD39 upregulation by Th17. Boosting downstream effects of AHR via UCB or enhancing CD39-mediated ectoenzymatic activity might provide therapeutic options to address development of Th17 dysfunction in IBD.
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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.