ArticleThe Journal of clinical investigation2014
Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 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
86 citing papers in PubMed, 132 citations in OpenAlex.
- Ischemic Stroke and Traumatic Brain Injury: Epidemiology, Molecular Pathways, and Emerging Therapies.MedComm · 2026Review
- Clinical risk factors for recurrence in adult-onset myelin oligodendrocyte glycoprotein antibody-associated optic neuritis.BMC ophthalmology · 2026Article
- Inhibition of endothelial S1PR2 preserves blood-brain barrier integrity after traumatic brain injury through activating the PI3K-AKT signaling pathway.Molecular and cellular biochemistry · 2026Article
- Discovery and in vivo evaluation of a fluorine-18 pro-drug tracer for imaging sphingosine-1-phosphate receptor 2 in the brain.Bioorganic & medicinal chemistry · 2026Article
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- Sphingolipid Metabolism in the Pathogenesis of Hashimoto's Thyroiditis.International journal of molecular sciences · 2025Review
- Revolutionizing Autoimmune Research: The Role of Caveolin-1.Immunity, inflammation and disease · 2025Review
- Repeated naloxone-induced morphine withdrawal alters blood brain barrier and blood spinal cord barrier integrity in mice.Molecular brain · 2025Article
- Sphingosine-1-Phosphate Modulation in Neurological Disorders: Insights from MS and Stroke.Brain sciences · 2025Review
- Bile acid metabolism in multiple sclerosis is perturbed and associated with the risk of confirmed disability worsening.BMC medicine · 2025Article
- Deciphering the role of sphingosine 1-phosphate in central nervous system myelination and repair.Journal of neurochemistry · 2025Review
- A Brain Endothelial Cell Caveolin-1/CXCL10 Axis Promotes T Cell Transcellular Migration Across the Blood-Brain Barrier.ASN neuro · 2025Article
- Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease.Journal of neurology, neurosurgery, and psychiatry · 2024Article
- Sided Stimulation of Endothelial Cells Modulates Neutrophil Trafficking in an In Vitro Sepsis Model.Advanced healthcare materials · 2024Article
- Expression of Inflammatory Mediators in Biofilm Samples and Clinical Association in Multiple Sclerosis Patients in Remission-A Pilot Study.Life (Basel, Switzerland) · 2024Article
- The Cellular Dysfunction of the Brain-Blood Barrier from Endothelial Cells to Astrocytes: The Pathway towards Neurotransmitter Impairment in Schizophrenia.International journal of molecular sciences · 2024Review
- The Current Landscape in the Development of Small-molecule Modulators Targeting Sphingosine-1-phosphate Receptors to Treat Neurodegenerative Diseases.Current topics in medicinal chemistry · 2024Review
- Electroacupuncture Alleviates Cerebral Ischemia-reperfusion Injury by Regulating the S1PR2/TLR4/NLRP3 Signaling Pathway via m6A Methylation of lncRNA H19.Current neurovascular research · 2024Article
- Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?International journal of molecular sciences · 2023Review
- Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.Pharmacology & therapeutics · 2023Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Multiple sclerosis (MS) is an inflammatory disease of the CNS that is characterized by BBB dysfunction and has a much higher incidence in females. Compared with other strains of mice, EAE in the SJL mouse strain models multiple features of MS, including an enhanced sensitivity of female mice to disease; however, the molecular mechanisms that underlie the sex- and strain-dependent differences in disease susceptibility have not been described. We identified sphingosine-1-phosphate receptor 2 (S1PR2) as a sex- and strain-specific, disease-modifying molecule that regulates BBB permeability by destabilizing adherens junctions. S1PR2 expression was increased in disease-susceptible regions of the CNS of both female SJL EAE mice and female patients with MS compared with their male counterparts. Pharmacological blockade or lack of S1PR2 signaling decreased EAE disease severity as the result of enhanced endothelial barrier function. Enhanced S1PR2 signaling in an in vitro BBB model altered adherens junction formation via activation of Rho/ROCK, CDC42, and caveolin endocytosis-dependent pathways, resulting in loss of apicobasal polarity and relocation of abluminal CXCL12 to vessel lumina. Furthermore, S1PR2-dependent BBB disruption and CXCL12 relocation were observed in vivo. These results identify a link between S1PR2 signaling and BBB polarity and implicate S1PR2 in sex-specific patterns of disease during CNS autoimmunity.
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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.