ArticleThe Journal of clinical investigation2016
Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Combining Machine Learning, Single-Cell Sequencing Data, and Mendelian Randomization Studies to Explore the Correlation Between Ischemic Stroke and Inflammatory Pathway Genes.International journal of genomics · 2026Article
- Identification of Disulfidptosis-Related Genes in Ischemic Stroke by Combining Single-Cell Sequencing, Machine Learning Algorithms, and In Vitro Experiments.Neuromolecular medicine · 2024Article
- The immunomodulatory mechanism of acupuncture treatment for ischemic stroke: research progress, prospects, and future direction.Frontiers in immunology · 2024Review
- Article
- A cross-species approach using an in vivo evaluation platform in mice demonstrates that sequence variation in human RABEP2 modulates ischemic stroke outcomes.American journal of human genetics · 2022Article
- CXCL13 expressed on inflamed cerebral blood vessels recruit IL-21 producing TJournal of neuroinflammation · 2022Article
- Interleukins and Ischemic Stroke.Frontiers in immunology · 2022Review
- γδ T Cell in Cerebral Ischemic Stroke: Characteristic, Immunity-Inflammatory Role, and Therapy.Frontiers in neurology · 2022Review
- New Directions in Therapeutic Angiogenesis and Arteriogenesis in Peripheral Arterial Disease.Circulation research · 2021Review
- Decreased granzyme BAmerican journal of cancer research · 2021Article
- T Cell Response in Ischemic Stroke: From Mechanisms to Translational Insights.Frontiers in immunology · 2021Review
- A Neuroprotective Locus Modulates Ischemic Stroke Infarction Independent of Collateral Vessel Anatomy.Frontiers in neuroscience · 2021Article
- Genetically Encoded Tools for Research of Cell Signaling and Metabolism under Brain Hypoxia.Antioxidants (Basel, Switzerland) · 2020Review
- Novel Neuroprotective Loci Modulating Ischemic Stroke Volume in Wild-Derived Inbred Mouse Strains.Genetics · 2019Article
- A Genome-Wide Analysis of the Penumbral Volume in Inbred Mice following Middle Cerebral Artery Occlusion.Scientific reports · 2019Article
- Choline acetyltransferase-expressing T cells are required to control chronic viral infection.Science (New York, N.Y.) · 2019Article
- Neuronal IL-4Rα modulates neuronal apoptosis and cell viability during the acute phases of cerebral ischemia.The FEBS journal · 2018Article
- BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.Circulation · 2017Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Risk for ischemic stroke has a strong genetic basis, but heritable factors also contribute to the extent of damage after a stroke has occurred. We previously identified a locus on distal mouse chromosome 7 that contributes over 50% of the variation in postischemic cerebral infarct volume observed between inbred strains. Here, we used ancestral haplotype analysis to fine-map this locus to 12 candidate genes. The gene encoding the IL-21 receptor (Il21r) showed a marked difference in strain-specific transcription levels and coding variants in neonatal and adult cortical tissue. Collateral vessel connections were moderately reduced in Il21r-deficient mice, and cerebral infarct volume increased 2.3-fold, suggesting that Il21r modulates both collateral vessel anatomy and innate neuroprotection. In brain slice explants, oxygen deprivation (OD) activated apoptotic pathways and increased neuronal cell death in IL-21 receptor-deficient (IL-21R-deficient) mice compared with control animals. We determined that the neuroprotective effects of IL-21R arose from signaling through JAK/STAT pathways and upregulation of caspase 3. Thus, natural genetic variation in murine Il21r influences neuronal cell viability after ischemia by modulating receptor function and downstream signal transduction. The identification of neuroprotective genes based on naturally occurring allelic variations has the potential to inform the development of drug targets for ischemic stroke treatment.
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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 Socratic graph.