ArticleThe Journal of clinical investigation2013
Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The trial behind it
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Who cites it
57 citing papers in PubMed, 123 citations in OpenAlex.
- The IL18RAP region disease polymorphism decreases IL-18RAP/IL-18R1/IL-1R1 expression and signaling through innate receptor-initiated pathways.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Structural and functional consequences of IL33 and IL1RL1 coding variants on IL-33/ST2 signaling.Genes and immunity · 2026Article
- Article
- Dual and context-dependent role of the interleukin-33/soluble suppression of tumorigenicity 2 axis in obesity and adipose tissue inflammation.Molecular medicine (Cambridge, Mass.) · 2026Article
- Genome-wide Association Study IdentifiesAllergy, asthma & immunology research · 2026Article
- Family-based genetics identifies association of CUBN, IL1RL1 and PRKN variants with leprosy in Bangladesh.Scientific reports · 2025Article
- Analysis of blood proteome in influenza-infected patients reveals new insights into the host response signatures distinguishing mild severe infections.Frontiers in immunology · 2025Article
- Epithelial Interleukin-1 Receptor-Like-1 Activation Is Contingent on Interleukin-33 Isoforms and Asthma-Related Receptor Variation.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2024Article
- IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Deciphering Early-Stage Molecular Mechanisms of Negative Pressure Wound Therapy in a Murine Model.International journal of molecular sciences · 2024Article
- Reducing decoys focuses fighting microglia.Nature aging · 2022Article
- An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer's disease.Nature aging · 2022Article
- Synergistic Effects of Weighted Genetic Risk Scores and Resistin and sST2 Levels on the Prognostication of Long-Term Outcomes in Patients with Coronary Artery Disease.International journal of molecular sciences · 2022Article
- Interleukin 1 receptor-like 1 rs13408661/13431828 polymorphism is associated with persistent post-bronchiolitis asthma at school age.Acta paediatrica (Oslo, Norway : 1992) · 2022Article
- Mitochondrial Pathophysiology on Chronic Kidney Disease.International journal of molecular sciences · 2022Review
- Coding and regulatory variants are associated with serum protein levels and disease.Nature communications · 2022Article
- Quantile-Specific Heritability of Inflammatory and Oxidative Stress Biomarkers Linked to Cardiovascular Disease.Journal of inflammation research · 2022Article
- Altered mRNA Expression of Interleukin-1 Receptors in Myocardial Tissue of Patients with Left Ventricular Assist Device Support.Journal of clinical medicine · 2021Article
- Analysis and Validation of Human Targets and Treatments Using a Hepatocellular Carcinoma-Immune Humanized Mouse Model.Hepatology (Baltimore, Md.) · 2021Article
- The Role of Galectin-3 and ST2 in Cardiology: A Short Review.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
27 authors at 7 institutions in 4 countries.
Funding
Abstract
The suppression of tumorigenicity 2/IL-33 (ST2/IL-33) pathway has been implicated in several immune and inflammatory diseases. ST2 is produced as 2 isoforms. The membrane-bound isoform (ST2L) induces an immune response when bound to its ligand, IL-33. The other isoform is a soluble protein (sST2) that is thought to be a decoy receptor for IL-33 signaling. Elevated sST2 levels in serum are associated with an increased risk for cardiovascular disease. We investigated the determinants of sST2 plasma concentrations in 2,991 Framingham Offspring Cohort participants. While clinical and environmental factors explained some variation in sST2 levels, much of the variation in sST2 production was driven by genetic factors. In a genome-wide association study (GWAS), multiple SNPs within IL1RL1 (the gene encoding ST2) demonstrated associations with sST2 concentrations. Five missense variants of IL1RL1 correlated with higher sST2 levels in the GWAS and mapped to the intracellular domain of ST2, which is absent in sST2. In a cell culture model, IL1RL1 missense variants increased sST2 expression by inducing IL-33 expression and enhancing IL-33 responsiveness (via ST2L). Our data suggest that genetic variation in IL1RL1 can result in increased levels of sST2 and alter immune and inflammatory signaling through the ST2/IL-33 pathway.
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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.