ArticleThe Journal of clinical investigation2019
P2Y6 signaling in alveolar macrophages prevents leukotriene-dependent type 2 allergic lung inflammation.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed, 27 citations in OpenAlex.
- Mast cell-specific CysLT2 receptor signaling inhibits cysteinyl leukotriene-dependent mast cell activation and type 2 allergic lung inflammation.Cell reports · 2026Article
- IL-Mediated Macrophage Polarization Axis: From Inflammatory Positive Feedback Loop to Precision Biomarkers and Therapeutic Targets for Allergic Rhinitis-A Narrative Review.Journal of asthma and allergy · 2026Review
- P2 Receptors as Therapeutic Targets in Allergic Rhinitis: Insights From the Use of Natural Products and Preclinical Studies.Journal of immunology research · 2026Review
- Unraveling cysteinyl leukotrienes and their receptors in inflammation through the brain-gut-lung axis.Virulence · 2025Review
- The Role of Uridine in Health and Disease.Journal of inflammation research · 2025Review
- Does Adenosine Triphosphate via Purinergic Receptor Signalling Fuel Pulmonary Fibrosis?Journal of innate immunity · 2025Review
- CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus.Frontiers in immunology · 2025Article
- Article
- Time to Rethink Bronchiolitis Obliterans Syndrome Following Lung or Hematopoietic Cell Transplantation in Pediatric Patients.Cancers · 2024Review
- Pyrimidinergic receptor P2Y6 expression is elevated in lung adenocarcinoma and is associated with poor prognosis.Cancer biomarkers : section A of Disease markers · 2023Article
- Macrophage P2Y6 Receptor Signaling Selectively Activates NFATC2 and Suppresses Allergic Lung Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Structure activity relationship of 3-nitro-2-(trifluoromethyl)-2H-chromene derivatives as P2YBioorganic & medicinal chemistry letters · 2021Article
- Review
- Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma?Frontiers in allergy · 2021Review
- Baicalin inhibits LPS-induced inflammation in RAW264.7 cells through miR-181b/HMGB1/TRL4/NF-κB pathway.American journal of translational research · 2021Article
- Metabolites Profiling of Melanoma Interstitial Fluids Reveals Uridine Diphosphate as Potent Immune Modulator Capable of Limiting Tumor Growth.Frontiers in cell and developmental biology · 2021Article
- Modulation of P2YScientific reports · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Antagonists of the type 1 cysteinyl leukotriene receptor (CysLT1R) are widely used to treat asthma and allergic rhinitis, with variable response rates. Alveolar macrophages express UDP-specific P2Y6 receptors that can be blocked by off-target effects of CysLT1R antagonists. Sensitizing intranasal doses of an extract from the house dust mite Dermatophagoides farinae (Df) sharply increased the levels of UDP detected in bronchoalveolar lavage fluid of mice. Conditional deletion of P2Y6 receptors before sensitization exacerbated eosinophilic lung inflammation and type 2 cytokine production in response to subsequent Df challenge. P2Y6 receptor signaling was necessary for dectin-2-dependent production of protective IL-12p40 and Th1 chemokines by alveolar macrophages, leading to activation of NK cells to generate IFN-γ. Administration of CysLT1R antagonists during sensitization blocked UDP-elicited potentiation of IL-12p40 production by macrophages in vitro, suppressed the Df-induced production of IL-12p40 and IFN-γ in vivo, and suppressed type 2 inflammation only in P2Y6-deficient mice. Thus, P2Y6 receptor signaling drives an innate macrophage/IL-12/NK cell/IFN-γ axis that prevents inappropriate allergic type 2 immune responses on respiratory allergen exposure and counteracts the Th2 priming effect of CysLT1R signaling at sensitization. Targeting P2Y6 signaling might prove to be a potential additional treatment strategy for allergy.
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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 Socratic graph.