ArticleThe Journal of clinical investigation2021
UDP-glucose and P2Y14 receptor amplify allergen-induced airway eosinophilia.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- A Systematic Review of the Role of Purinergic Signalling Pathway in the Treatment of COVID-19.International journal of molecular sciences · 2023Pooled it
- Purinergic signaling in osteoarthritis: Mechanistic insights into pathogenesis and therapeutic targeting.Genes & diseases · 2026Review
- UDP-Glucose-P2Y14 Receptor Signaling Enhances the Responsiveness of Hematopoietic Stem/Progenitor Cells to Chemoattractants by Facilitating Membrane Lipid Raft Formation and Nlrp3 Inflammasome Activation.Stem cell reviews and reports · 2026Article
- P2Y14 receptor activation and neutrophil signaling: linking inflammation to systemic pathophysiology.Purinergic signalling · 2026Review
- Millettia speciosa reprograms the lung proteome and suppresses CCL24-driven eosinophilic inflammation in allergic asthma.Frontiers in allergy · 2026Article
- Article
- UDP-glucose and MRS2905 agonist-bound states of the purinergic P2YCommunications biology · 2025Article
- P2YACS pharmacology & translational science · 2025Article
- UDP-glucose regulates dendritic cell mitochondrial respiration via a nitric oxide-dependent mechanism.Journal of leukocyte biology · 2025Article
- E. B. Hershberg Award: Taming Inflammation by Tuning Purinergic Signaling.Accounts of chemical research · 2025Article
- Diabetes mellitus-driven pulmonary injury: multidimensional mechanisms linking metabolic dysregulation to gut-lung axis and promising therapies.Frontiers in pharmacology · 2025Review
- Advancing toward a unified eosinophil signature from transcriptional profiling.Journal of leukocyte biology · 2024Review
- Pharmacometabolomics Approach to Explore Pharmacokinetic Variation and Clinical Characteristics of a Single Dose of Desvenlafaxine in Healthy Volunteers.Pharmaceutics · 2024Article
- Chimeras Derived from a P2YACS pharmacology & translational science · 2024Article
- Hematopoietic and eosinophil-specific LNK(SH2B3) deficiency promotes eosinophilia and arterial thrombosis.Blood · 2024Article
- Chemokine CCL19 promotes type 2 T-cell differentiation and allergic airway inflammation.The Journal of allergy and clinical immunology · 2024Article
- OsUGE2 Regulates Plant Growth through Affecting ROS Homeostasis and Iron Level in Rice.Rice (New York, N.Y.) · 2024Article
- Clinical characteristics and factors associated with mucus plugs under bronchoscopy in children hospitalized for acute asthma attack.Frontiers in pediatrics · 2024Article
- Air pollution exposure is associated with gene expression in children.Environmental epigenetics · 2024Article
- Qizhu Rougan Granules suppress liver fibrosis by inhibiting the expression of the P2Y14 receptor on hepatic stellate cells.Frontiers in pharmacology · 2024Article
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Airway eosinophilia is a hallmark of allergic asthma and is associated with mucus production, airway hyperresponsiveness, and shortness of breath. Although glucocorticoids are widely used to treat asthma, their prolonged use is associated with several side effects. Furthermore, many individuals with eosinophilic asthma are resistant to glucocorticoid treatment, and they have an unmet need for novel therapies. Here, we show that UDP-glucose (UDP-G), a nucleotide sugar, is selectively released into the airways of allergen-sensitized mice upon their subsequent challenge with that same allergen. Mice lacking P2Y14R, the receptor for UDP-G, had decreased airway eosinophilia and airway hyperresponsiveness compared with wild-type mice in a protease-mediated model of asthma. P2Y14R was dispensable for allergic sensitization and for the production of type 2 cytokines in the lung after challenge. However, UDP-G increased chemokinesis in eosinophils and enhanced their response to the eosinophil chemoattractant, CCL24. In turn, eosinophils triggered the release of UDP-G into the airway, thereby amplifying eosinophilic recruitment. This positive feedback loop was sensitive to therapeutic intervention, as a small molecule antagonist of P2Y14R inhibited airway eosinophilia. These findings thus reveal a pathway that can be therapeutically targeted to treat asthma exacerbations and glucocorticoid-resistant forms of this disease.
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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.