ArticleThe Journal of biological chemistry2016
Interleukin 2 Activates Brain Microvascular Endothelial Cells Resulting in Destabilization of Adherens Junctions.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
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- Antigen-IL-2 CAR-enhancer drives CAR-T fate and stemness, enhancing antitumor efficacy across models independent of IL-2Rα.Journal for immunotherapy of cancer · 2026Article
- Whole blood TNF-α expression and apoptotic endothelial microparticles reveal early vascular injury in pediatric obesity.International journal of obesity (2005) · 2026Article
- Persistent neurological and behavioral alterations after SARS-CoV-2 infection in an optimized K18-hACE2 mouse model.Frontiers in microbiology · 2026Article
- An immune competent in vitro model of IL2 induced vascular leakage enables mechanistic insights and evaluation of mitigation strategies.Scientific reports · 2025Article
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- Breaking the Barrier: The Role of Proinflammatory Cytokines in BBB Dysfunction.International journal of molecular sciences · 2025Review
- Endothelial Dysfunctions in Blood-Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies.CNS neuroscience & therapeutics · 2024Review
- Review
- Homocysteine potentiates amyloidAging cell · 2024Article
- IL-2 based cancer immunotherapies: an evolving paradigm.Frontiers in immunology · 2024Review
- IL-2-driven CD8Trends in immunology · 2023Review
- Inflammatory cytokines as mediators of retinal endothelial barrier dysfunction in non-infectious uveitis.Clinical & translational immunology · 2023Review
- The role of primed and non-primed MSC-derived conditioned media in neuroregeneration.Frontiers in molecular neuroscience · 2023Article
- Effective Combination Immunotherapy with Oncolytic Adenovirus and Anti-PD-1 for Treatment of Human and Murine Ovarian Cancers.Diseases (Basel, Switzerland) · 2022Article
- Further Evidence of Neuroprotective Effects of Recombinant Human Erythropoietin and Growth Hormone in Hypoxic Brain Injury in Neonatal Mice.International journal of molecular sciences · 2022Article
- Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation.Nature immunology · 2022Article
- RNA-Seq Profiling of Neutrophil-Derived Microvesicles in Alzheimer's Disease Patients Identifies a miRNA Signature That May Impact Blood-Brain Barrier Integrity.International journal of molecular sciences · 2022Article
- Impact of Non-pharmacological Chronic Hypertension on a Transgenic Rat Model of Cerebral Amyloid Angiopathy.Frontiers in neuroscience · 2022Article
- Transient Opening of the Blood-Brain Barrier by Vasoactive Peptides to Increase CNS Drug Delivery: Reality Versus Wishful Thinking?Current neuropharmacology · 2022Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
The pleiotropic cytokine interleukin 2 (IL2) disrupts the blood-brain barrier and alters brain microcirculation, underlying vascular leak syndrome that complicates cancer immunotherapy with IL2. The microvascular effects of IL2 also play a role in the development of multiple sclerosis and other chronic neurological disorders. The mechanism of IL2-induced disruption of brain microcirculation has not been determined previously. We found that both human and murine brain microvascular endothelial cells express constituents of the IL2 receptor complex. Then we established that signaling through this receptor complex leads to activation of the transcription factor, nuclear factor κB, resulting in expression of proinflammatory interleukin 6 and monocyte chemoattractant protein 1. We also discovered that IL2 induces disruption of adherens junctions, concomitant with cytoskeletal reorganization, ultimately leading to increased endothelial cell permeability. IL2-induced phosphorylation of vascular endothelial cadherin (VE-cadherin), a constituent of adherens junctions, leads to dissociation of its stabilizing adaptor partners, p120-catenin and β-catenin. Increased phosphorylation of VE-cadherin was also accompanied by a reduction of Src homology 2 domain-containing protein-tyrosine phosphatase 2, known to maintain vascular barrier function. These results unravel the mechanism of deleterious effects induced by IL2 on brain microvascular endothelial cells and may inform the development of new measures to improve IL2 cancer immunotherapy, as well as treatments for autoimmune diseases affecting the central nervous system.
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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.