ArticleScience translational medicine2013
TGFβ receptor mutations impose a strong predisposition for human allergic disease.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02504853 (Natural History and Genetics of Food Allergy and Related Conditions), which is not on this map. Cited by 113 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.
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.
Natural History and Genetics of Food Allergy and Related Conditions
Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 217 citations in OpenAlex.
- The relationship between interleukin-18 polymorphisms and allergic disease: a meta-analysis.BioMed research international · 2014Pooled it
- Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis.The journal of allergy and clinical immunology. In practice · 2024Trial
- Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome.The Journal of allergy and clinical immunology · 2014Trial
- Exploring Biomarkers and Regulatory Mechanisms Associated with Lytic Cell Death in Allergic Rhinitis Based on Transcriptome Analysis.Biomedicines · 2026Article
- Mixed Signals: T Cells as Architects of IgE Immunity.Immunological reviews · 2026Review
- Immune functions of the esophagus.The Journal of allergy and clinical immunology · 2026Review
- Gut mucosal immune responses - Implications for celiac disease and food allergy.Seminars in immunology · 2025Review
- Microplastic exposure in the lungs of young children and its associations with allergic rhinitis: A cross-sectional study in China.Eco-Environment & Health · 2025Article
- The oesophagus as an immune organ.Nature reviews. Gastroenterology & hepatology · 2025Review
- Loeys-Dietz Syndrome and Asthma: Pathophysiological Insights and Clinical Dilemmas.Respirology case reports · 2025Article
- Pathological IgE Production in Inborn Errors of Immunity and Beyond.Immunological reviews · 2025Review
- Association between systemic inflammatory response index and eczema among children and adolescents: a cross-sectional study based on NHANES database.Frontiers in pediatrics · 2025Article
- The genetics of hyper IgE syndromes.Frontiers in immunology · 2025Review
- Understanding and Managing Hyper IgE Syndromes.ImmunoTargets and therapy · 2025Review
- Insights into the clinical, immunologic, and genetic underpinnings of food allergy.Immunological reviews · 2024Review
- TThe Journal of allergy and clinical immunology · 2024Review
- Investigating dysregulation of TGF-β1/SMAD3 signaling in atopic dermatitis: a molecular and immunohistochemical analysis.Clinical and experimental immunology · 2024Article
- Polymorphic markers of several immune regulatory genes modulate the susceptibility for eczema and related phenotypes in children.Translational pediatrics · 2024Article
- Causal relationship between immunophenotypes and mitral valve prolapse: a bidirectional Mendelian randomization study.Frontiers in cardiovascular medicine · 2024Article
- Cardiovascular complications in vascular connective tissue disorders after COVID-19 infection and vaccination.PloS one · 2024Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Transforming growth factor-β (TGFβ) is a multifunctional cytokine that plays diverse roles in physiologic processes as well as human disease, including cancer, heart disease, and fibrotic disorders. In the immune system, TGFβ regulates regulatory T cell (Treg) maturation and immune homeostasis. Although genetic manipulation of the TGFβ pathway modulates immune tolerance in mouse models, the contribution of this pathway to human allergic phenotypes is not well understood. We demonstrate that patients with Loeys-Dietz syndrome (LDS), an autosomal dominant disorder caused by mutations in the genes encoding receptor subunits for TGFβ, TGFBR1 and TGFBR2, are strongly predisposed to develop allergic disease, including asthma, food allergy, eczema, allergic rhinitis, and eosinophilic gastrointestinal disease. LDS patients exhibited elevated immunoglobulin E levels, eosinophil counts, and T helper 2 (TH2) cytokines in their plasma. They had an increased frequency of CD4(+) T cells that expressed both Foxp3 and interleukin-13, but retained the ability to suppress effector T cell proliferation. TH2 cytokine-producing cells accumulated in cultures of naïve CD4(+) T cells from LDS subjects, but not controls, after stimulation with TGFβ, suggesting that LDS mutations support TH2 skewing in naïve lymphocytes in a cell-autonomous manner. The monogenic nature of LDS demonstrates that altered TGFβ signaling can predispose to allergic phenotypes in humans and underscores a prominent role for TGFβ in directing immune responses to antigens present in the environment and foods. This paradigm may be relevant to nonsyndromic presentations of allergic disease and highlights the potential therapeutic benefit of strategies that inhibit TGFβ signaling.
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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.