ArticleJournal of autoimmunity2018
HIF-1α-induced xenobiotic transporters promote Th17 responses in Crohn's disease.
Article in Journal of autoimmunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Impact of C-reactive protein on the effect of Roxadustat for the treatment of anemia in chronic kidney disease: a systematic review of randomized controlled trials.BMC nephrology · 2024Pooled it
- Inhibition of estrogen receptor alpha stabilizes regulatory T cell function in autoimmune hepatitis.JHEP reports : innovation in hepatology · 2026Article
- Hypoxia-Inducible Factor 1-α in Autoimmune Diseases-Insights from the Paradigm of Hashimoto's Thyroiditis: A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- The central regulator HIF-1α in digestive system pathologies: inflammation and cancer.Frontiers in immunology · 2026Review
- Hepatic Arachidonic Acid Dysregulation Impairs Double-Negative Regulatory T Cell-Mediated Immunoregulation via CD39 Downregulation and Drives MASLD Development.Journal of immunology research · 2026Article
- Antisense to human CD39 dysregulates immune metabolism in inflammatory bowel disease.Cellular & molecular immunology · 2025Article
- Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease.Scientific reports · 2025Article
- Network pharmacology, molecular docking, and untargeted metabolomics reveal molecular mechanisms of multi-targets effects of Qingfei Tongluo Plaster improving respiratory syncytial virus pneumonia.Chinese herbal medicines · 2024Article
- Oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles attenuates gastric and small intestinal mucosal ferroptosis caused by hypoxia through inhibiting HIF-1α- and HIF-2α-mediated lipid peroxidation.Journal of nanobiotechnology · 2024Article
- Silencing of aryl hydrocarbon receptor repressor restrains Th17 cell immunity in autoimmune hepatitis.Journal of autoimmunity · 2024Article
- Recent Advances in Hepatic Metabolic Regulation by the Nuclear Factor Rev-erbɑ.Current drug metabolism · 2024Review
- Hypoxia, hypoxia-inducible factors and inflammatory bowel diseases.Gastroenterology report · 2024Review
- Aryl hydrocarbon receptor: current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases.Frontiers in immunology · 2024Review
- High and Low Levels ofInternational journal of molecular sciences · 2023Article
- Mitochondrial dysfunctions in T cells: focus on inflammatory bowel disease.Frontiers in immunology · 2023Review
- ATP-dependent transporters: emerging players at the crossroads of immunity and metabolism.Frontiers in immunology · 2023Review
- Research progress on the mechanism of cholesterol-25-hydroxylase in intestinal immunity.Frontiers in immunology · 2023Review
- Blockade of PGK1 and ALDOA enhances bilirubin control of Th17 cells in Crohn's disease.Communications biology · 2022Article
- Tumour Microenvironment Stress Promotes the Development of Drug Resistance.Antioxidants (Basel, Switzerland) · 2021Review
- Limited TCR repertoire andiScience · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
In Crohn's disease, pathogenic Th17-cells express low levels of CD39 ectonucleotidase and are refractory to the immunosuppressive effects of unconjugated bilirubin (UCB), an endogenous ligand for aryl-hydrocarbon-receptor (AhR). This resistance to AhR ligation might be associated with alterations in responses to hypoxia. Limited exposure to hypoxia appears beneficial in acute tissue injury. However, in protracted inflammation, hypoxemia may paradoxically result in Th17-cell activation. We report here that in vitro exposure of Th17-cells from Crohn's disease patients to hypoxia limits responsiveness to AhR stimulation by UCB, as reflected by lower CD39 levels. Blockade of hypoxia-inducible-factor-1alpha (HIF-1α) upregulates CD39 and favors Th17-cell regulatory responses. Resistance of Th17-cells to AhR signaling results, in part, from HIF-1α-dependent induction of ATP-binding cassette (ABC) transporters: multidrug-resistance-protein-1 (MDR1) and multidrug-resistance-associated-protein-4 (MRP4). Increased ABC transporters promote efflux of suppressive AhR ligands, such as UCB, from Th17-cells. Inhibition of MDR1, MRP4 and/or HIF-1α with ritonavir (RTV) reconstitutes AhR function in Th17-cells, enhancing therapeutic effects of UCB in dextran-sulfate-sodium-induced experimental colitis. Deleterious effects of hypoxia on Th17-cells in Crohn's disease can be ameliorated either by inhibiting HIF-1α or by suppressing ABC transporters to increase UCB availability as an AhR substrate. Targeting HIF-1α-ABC transporters could provide innovative therapeutic pathways for 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.