ArticleJCI insight2020
Siponimod therapy implicates Th17 cells in a preclinical model of subpial cortical injury.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Lymphotoxin-dependent elevated meningeal CXCL13:BAFF ratios drive gray matter injury.Nature immunology · 2026Article
- Follicle on the Roof: Tertiary Lymphoid Structures in Central Nervous System Autoimmunity.Immunological reviews · 2025Review
- Towards Treating Multiple Sclerosis Progression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Characterization of cortico-meningeal translocator protein expression in multiple sclerosis.Brain : a journal of neurology · 2024Article
- FirstTheranostics · 2023Article
- Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis.International journal of molecular sciences · 2022Article
- Age-dependent gray matter demyelination is associated with leptomeningeal neutrophil accumulation.JCI insight · 2022Article
- Increased Remyelination and Proregenerative Microglia Under Siponimod Therapy in Mechanistic Models.Neurology(R) neuroimmunology & neuroinflammation · 2022Article
- Accumulation of meningeal lymphocytes correlates with white matter lesion activity in progressive multiple sclerosis.JCI insight · 2022Article
- Mechanism-based criteria to improve therapeutic outcomes in progressive multiple sclerosis.Nature reviews. Neurology · 2022Review
- Review
- Critical Roles of Lysophospholipid Receptors in Activation of Neuroglia and Their Neuroinflammatory Responses.International journal of molecular sciences · 2021Review
- Imaging meningeal inflammation in CNS autoimmunity identifies a therapeutic role for BTK inhibition.Brain : a journal of neurology · 2021Article
- Review
- Inflammatory mechanisms underlying cortical injury in progressive multiple sclerosis.Neuroimmunology and neuroinflammation · 2021Article
- Review
- An "Outside-In" and "Inside-Out" Consideration of Complement in the Multiple Sclerosis Brain: Lessons From Development and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Subpial demyelination is a specific hallmark of multiple sclerosis and a correlate of disease progression. Although the mechanism(s) that mediate pathogenesis in the subpial compartment remain unclear, it has been speculated that inflammation in the overlying meninges may be associated with subpial injury. Here we show that adoptive transfer of proteolipid protein-primed Th17 cells into SJL/J recipient mice induces subpial demyelination associated with microglial/macrophage activation, disruption of the glial limitans, and evidence of an oxidative stress response. This pathology was topologically associated with foci of immune cells in the meninges and occurred in the absence of measurable anti-myelin oligodendrocyte glycoprotein IgM or IgG antibodies. To test the role of brain-infiltrating leukocytes on subpial injury, we modulated sphingosine 1-phosphate (S1P) receptor1,5 activity with BAF312 (siponimod) treatment. Administration of BAF312, even after adoptively transferred T cells had entered the brain, significantly ameliorated clinical experimental autoimmune encephalomyelitis and diminished subpial pathology, concomitant with a selective reduction in the capacity of transferred T cells to make Th17 cytokines. We conclude that sustained subpial cortical injury is associated with the capacity for brain-resident T cells to produce Th17 cytokines, and this pathological process occurs in an S1P receptor1,5-dependent manner.
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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.