ArticleJournal of neuroinflammation2023
Sequential treatment with a TNFR2 agonist and a TNFR1 antagonist improves outcomes in a humanized mouse model for MS.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Neuro-Behavioral Improvement and Mechanistic Pathways of Bone Marrow-Derived Mesenchymal Stem Cells and Exosomes in Experimental Multiple Sclerosis: A Systematic Review and Meta-analysis.Cellular and molecular neurobiology · 2026Pooled it
- Mapping the TNFR2-targeting antibody patent landscape: Insights from macro trends to structural signatures.Human vaccines & immunotherapeutics · 2026Article
- Neuroinflammation and Graft Survival in Pluripotent Stem Cell-Derived Therapies for the Central Nervous System.Journal of neurochemistry · 2026Review
- Soluble tumor necrosis factor receptors in diabetes: risk sensing and receptor-resolved targeting.Endocrine journal · 2026Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Cell death in multiple sclerosis.Cell death and differentiation · 2026Review
- Upregulation of TNFR2 Precedes TOX Expression by Exhausted T cells and Restricts Antitumor and Antiviral Immunity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Chorioamnionitis Induces a Unique Time Course of Inflammatory Changes and Immune Reponses in the Brain and Spleen.Developmental neuroscience · 2026Article
- TNFR2 Agonism: Basic Science and Promising Treatment for Multiple Sclerosis and Related Diseases.International journal of molecular sciences · 2025Review
- Single intracerebroventricular TNFR2 agonist injection impacts remyelination in the cuprizone model.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Sex-chromosome complement and Activin-A shape the therapeutic potential of TNFR2 activation in a model of MS and CNP.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway.Biomedicines · 2024Article
- Immunity impacts cognitive deficits across neurological disorders.Journal of neurochemistry · 2024Review
- Tumor necrosis factor receptor 2 activation elicits sex-specific effects on cortical myelin proteins and functional recovery in a model of multiple sclerosis.Brain research bulletin · 2024Article
- A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis.Biomedicines · 2023Review
- Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
TNF signaling is an essential regulator of cellular homeostasis. Through its two receptors TNFR1 and TNFR2, soluble versus membrane-bound TNF enable cell death or survival in a variety of cell types. TNF-TNFRs signaling orchestrates important biological functions such as inflammation, neuronal activity as well as tissue de- and regeneration. TNF-TNFRs signaling is a therapeutic target for neurodegenerative diseases such as multiple sclerosis (MS) and Alzheimer's disease (AD), but animal and clinical studies yielded conflicting findings. Here, we ask whether a sequential modulation of TNFR1 and TNFR2 signaling is beneficial in experimental autoimmune encephalomyelitis (EAE), an experimental mouse model that recapitulates inflammatory and demyelinating aspects of MS. To this end, human TNFR1 antagonist and TNFR2 agonist were administered peripherally at different stages of disease development in TNFR-humanized mice. We found that stimulating TNFR2 before onset of symptoms leads to improved response to anti-TNFR1 therapeutic treatment. This sequential treatment was more effective in decreasing paralysis symptoms and demyelination, when compared to single treatments. Interestingly, the frequency of the different immune cell subsets is unaffected by TNFR modulation. Nevertheless, treatment with only a TNFR1 antagonist increases T-cell infiltration in the central nervous system (CNS) and B-cell cuffing at the perivascular sites, whereas a TNFR2 agonist promotes Treg CNS accumulation. Our findings highlight the complicated nature of TNF signaling which requires a timely balance of selective activation and inhibition of TNFRs in order to exert therapeutic effects in the context of 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.