ArticleCellular & molecular immunology2019
Aryl hydrocarbon receptor signaling promotes ORMDL3-dependent generation of sphingosine-1-phosphate by inhibiting sphingosine-1-phosphate lyase.
Article in Cellular & molecular immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 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.
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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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Single-Cell Meta-Analysis Uncovers the Pancreatic Endothelial Cell Transcriptomic Signature and Reveals a Key Role for NKX2-3 in PLVAP Expression.Arteriosclerosis, thrombosis, and vascular biology · 2024Pooled it
- Multi-Dimensional Perspective of the Gene and Environmental Interaction in Asthma.Clinical reviews in allergy & immunology · 2026Review
- A Perspective on the Role of Metformin in Treating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID.ACS pharmacology & translational science · 2025Review
- Functional sequence variants of intergenic long noncoding RNA on chromosome 17q21 are associated with asthma.The European respiratory journal · 2025Article
- PLK1 Mediates the Proliferation and Contraction of Airway Smooth Muscle Cells and Has a Role in T2-High Asthma with Neutrophilic Inflammation Model.Journal of inflammation research · 2025Article
- Gut microbiota-host lipid crosstalk in Alzheimer's disease: implications for disease progression and therapeutics.Molecular neurodegeneration · 2024Review
- Activation of aryl hydrocarbon receptor (AhR) in Alzheimer's disease: role of tryptophan metabolites generated by gut host-microbiota.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation.International journal of biological sciences · 2023Article
- Aryl hydrocarbon receptor (AhR) reveals evidence of antagonistic pleiotropy in the regulation of the aging process.Cellular and molecular life sciences : CMLS · 2022Review
- Aryl hydrocarbon receptor: The master regulator of immune responses in allergic diseases.Frontiers in immunology · 2022Review
- The Aryl Hydrocarbon Receptor in Asthma: Friend or Foe?International journal of molecular sciences · 2020Review
- Review
- Glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- ORMDL3 and Asthma: Linking Sphingolipid Regulation to Altered T Cell Function.Frontiers in immunology · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Aryl hydrocarbon receptor (AhR), a cellular chemical sensor, controls cellular homeostasis, and sphingosine-1-phosphate (S1P), a bioactive intermediate of sphingolipid metabolism, is believed to have a role in immunity and inflammation, but their potential crosstalk is currently unknown. We aimed to determine whether there is a functional linkage between AhR signaling and sphingolipid metabolism. We showed that AhR ligands, including an environmental polycyclic aromatic hydrocarbon (PAH), induced S1P generation, and inhibited S1P lyase (S1PL) activity in resting cells, antigen/IgE-activated mast cells, and mouse lungs exposed to the AhR ligand alone or in combination with antigen challenge. The reduction of S1PL activity was due to AhR-mediated oxidation of S1PL at residue 317, which was reversible by the addition of an antioxidant or in cells with knockdown of the ORMDL3 gene encoding an ER transmembrane protein, whereas C317A S1PL mutant-transfected cells were resistant to the AhR-mediated effect. Furthermore, analysis of AhR ligand-treated cells showed a time-dependent increase of the ORMDL3-S1PL complex, which was confirmed by FRET analysis. This change increased the S1P levels, which in turn, induced mast cell degranulation via S1PR2 signaling. In addition, elevated levels of plasma S1P were found in children with asthma compared to non-asthmatic subjects. These results suggest a new regulatory pathway whereby the AhR-ligand axis induces ORMDL3-dependent S1P generation by inhibiting S1PL, which may contribute to the expression of allergic diseases.
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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.