ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Leukotriene E4 activates human Th2 cells for exaggerated proinflammatory cytokine production in response to prostaglandin D2.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 44 citations in OpenAlex.
- Biological effects of leukotriene E4 on eosinophils.Prostaglandins, leukotrienes, and essential fatty acids · 2014Trial
- Mast cell-specific CysLT2 receptor signaling inhibits cysteinyl leukotriene-dependent mast cell activation and type 2 allergic lung inflammation.Cell reports · 2026Article
- Roles of Lipoxygenases in Cardiovascular Diseases.Journal of cardiovascular translational research · 2025Review
- Cysteinyl Leukotrienes in Allergic Inflammation.Annual review of pathology · 2025Review
- Beyond CCR7: dendritic cell migration in type 2 inflammation.Frontiers in immunology · 2025Review
- Biofilm-derived oxylipin 10-HOME-mediated immune response in women with breast implants.The Journal of clinical investigation · 2023Article
- Phospholipid scramblase-1 regulates innate type 2 inflammation in mouse lungs via CRTH2-dependent mechanisms.The Journal of clinical investigation · 2023Article
- Polyunsaturated Fatty Acids and Their Immunomodulatory Actions in Periodontal Disease.Nutrients · 2023Review
- Regulatory Roles of Phospholipase AFrontiers in immunology · 2022Review
- Modulating the Blood-Brain Barrier: A Comprehensive Review.Pharmaceutics · 2021Review
- The Roles of Type 2 Cytotoxic T Cells in Inflammation, Tissue Remodeling, and Prostaglandin (PG) DJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Cytokine Storm and Mucus Hypersecretion in COVID-19: Review of Mechanisms.Journal of inflammation research · 2021Review
- G Protein-Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action.Pharmacological reviews · 2020Review
- Function of secreted phospholipase ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- Quantification of eicosanoids and their metabolites in biological matrices: a review.Bioanalysis · 2018Review
- The prostaglandin DRespiratory research · 2018Review
- Synergistic activation of pro-inflammatory type-2 CD8Mucosal immunology · 2018Article
- Orchestration of epithelial-derived cytokines and innate immune cells in allergic airway inflammation.Cytokine & growth factor reviews · 2018Review
- Cysteinyl leukotriene EThe Journal of allergy and clinical immunology · 2017Article
- Leukotriene C4 Potentiates IL-33-Induced Group 2 Innate Lymphoid Cell Activation and Lung Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
PGD(2) exerts a number of proinflammatory responses through a high-affinity interaction with chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and has been detected at high concentrations at sites of allergic inflammation. Because cysteinyl leukotrienes (cysLTs) are also produced during the allergic response, we investigated the possibility that cysLTs may modulate the response of human Th2 cells to PGD(2). PGD(2) induced concentration-dependent Th2 cytokine production in the absence of TCR stimulation. Leukotrienes D(4) and E(4) (LTE(4)) also stimulated the cytokine production but were much less active than PGD(2). However, when combined with PGD(2), cysLTs caused a greater than additive enhancement of the response, with LTE(4) being most effective in activating Th2 cells. LTE(4) enhanced calcium mobilization in response to PGD(2) in Th2 cells without affecting endogenous PGD(2) production or CRTH2 receptor expression. The effect of LTE(4) was inhibited by montelukast but not by the P2Y(12) antagonist methylthioadenosine 5'-monophosphate. The enhancing effect was also evident with endogenous cysLTs produced from immunologically activated mast cells because inhibition of cysLT action by montelukast or cysLT synthesis by MK886, an inhibitor of 5-lipoxygenase-activating protein, reduced the response of Th2 cells to the levels produced by PGD(2) alone. These findings reveal that cysLTs, in particular LTE(4), have a significant proinflammatory impact on T cells and demonstrate their effects on Th2 cells are mediated by a montelukast-sensitive receptor.
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