ArticleNature medicine2016
An asthma-associated IL4R variant exacerbates airway inflammation by promoting conversion of regulatory T cells to TH17-like cells.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03694158 (Effect of IL-4RαR576 Polymorphism on Response to Dupilumab in Asthma, a Genotype-stratified, Randomized, Placebo- Controlled Trial), which is not on this map. Cited by 126 papers.
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.
Effect of IL-4RαR576 Polymorphism on Response to Dupilumab in Asthma, a Genotype-stratified, Randomized, Placebo- Controlled Trial
Who cites it
126 citing papers in PubMed, 173 citations in OpenAlex.
- Gene-environment interaction between an IL4R variant and school endotoxin exposure contributes to asthma symptoms in inner-city children.The Journal of allergy and clinical immunology · 2018Trial
- Type 2 conventional dendritic cells and regulatory T cells form a barrier tissue circuit to control allergic inflammation.bioRxiv : the preprint server for biology · 2026Article
- Association between frailty and the risks of chronic pulmonary diseases and lung cancer.BMC pulmonary medicine · 2026Article
- MST1 bridges LYN and SHP-1 to suppress FcεRI-mediated mast cell activation and allergic responses.Cellular & molecular immunology · 2026Article
- The epigenetic-immune-microbiome axis in early life: reprogramming the origins and endotypes of pediatric asthma.Frontiers in immunology · 2026Review
- Decoding Treg diversity and dysfunction to advance Treg-based therapies in autoimmune and inflammatory diseases.Frontiers in immunology · 2026Review
- Prostaglandin IThe Journal of allergy and clinical immunology · 2025Article
- T Regulatory Mechanisms in Airway and Interstitial Lung Disease.Seminars in respiratory and critical care medicine · 2025Review
- Article
- SERPINB10 promotes macrophage M2 polarization and airway inflammation in asthma.Respiratory research · 2025Article
- Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM.Cell genomics · 2025Article
- Review
- Effects of Neutrophil-Activating Protein ofAdvanced biomedical research · 2025Article
- Regulatory T cells and their role in allergic disease.Allergy · 2025Review
- Targeting the IL-4/IL-4R Axis in Th2 Inflammatory Diseases: A Review of Clinical Efficacy and Safety.Journal of inflammation research · 2025Review
- The 'TNature reviews. Rheumatology · 2025Review
- Genetic Variant rs1801275 in Atopic Dermatitis: Prevalence and Clinical Implications in Vietnamese Population.Journal of asthma and allergy · 2025Article
- The immunobiology and therapeutic potential of regulatory T cells in autoimmune diseases and allergic diseases.Frontiers in immunology · 2025Review
- Recommendations for Clinicians to Combat Environmental Disparities in Pediatric Asthma: A Review.Chest · 2024Review
- LPG 18:0 is a general biomarker of asthma and inhibits the differentiation and function of regulatory T-cells.The European respiratory journal · 2024Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mechanisms by which regulatory T (Treg) cells fail to control inflammation in asthma remain poorly understood. We show that a severe asthma-associated polymorphism in the gene encoding the interleukin (IL)-4 receptor alpha chain (Il4ra(R576)) promotes conversion of induced Treg (iTreg) cells toward a T helper 17 (TH17) cell fate. This skewing is mediated by the recruitment by IL-4Rα(R576) of the growth-factor-receptor-bound protein 2 (GRB2) adaptor protein, which drives IL-17 expression by activating a pathway that involves extracellular-signal-regulated kinase, IL-6 and the transcription factor STAT3. Treg cell-specific deletion of genes that regulate TH17 cell differentiation, including Il6ra and RAR-related orphan receptor gamma (Rorc), but not of Il4 or Il13, prevented exacerbated airway inflammation in mice expressing Il4ra(R576) (hereafter referred to as Il4ra(R576) mice). Furthermore, treatment of Il4ra(R576) mice with a neutralizing IL-6-specific antibody prevented iTreg cell reprogramming into TH17-like cells and protected against severe airway inflammation. These findings identify a previously unknown mechanism for the development of mixed TH2-TH17 cell inflammation in genetically prone individuals and point to interventions that stabilize iTreg cells as potentially effective therapeutic strategies.
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What OpenQuestion holds
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.