ArticleJournal of autoimmunity2015
TNF-like weak inducer of apoptosis promotes blood brain barrier disruption and increases neuronal cell death in MRL/lpr mice.
Article in Journal of autoimmunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Circulating inflammatory proteins associated with risks of schizophrenia, bipolar disorder, and major depressive disorder: a mendelian randomization study.Translational psychiatry · 2025Pooled it
- The potential role of kynurenine pathway and inflammation in pediatric obsessive-compulsive disorder with and without major depressive disorder comorbidity.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Targeting microglial C1q alleviates blood-brain barrier disruption in the thalamus after cortical infarction.Journal of neuroinflammation · 2026Article
- Time‑resolved multi-omic analysis of paclitaxel exposure in human iPSC‑derived sensory neurons unveils mechanisms of chemotherapy‑induced peripheral neuropathy.Cell death & disease · 2026Article
- Sustained NPSLE-like phenotype in the absence of systemic lupus-like disease in TLR7-deficient B6.Nba2 mice.Brain, behavior, and immunity · 2025Article
- Neural circuit mechanisms underlying aberrantly prolonged functional hyperemia in young Alzheimer's disease mice.Molecular psychiatry · 2025Article
- A volumetric study of the choroid plexus in neuropsychiatric systemic lupus erythematosus.Scientific reports · 2025Article
- TWEAK-Fn14: a promising target for cardio-cerebrovascular diseases and brain-heart syndrome.Frontiers in immunology · 2025Review
- Biomarkers and therapeutic targets in early Alzheimer's disease: an Olink proteomics study.Frontiers in neurology · 2025Article
- The MRL Model: A Valuable Tool in Studies of Autoimmunity-Brain Interactions.Methods in molecular biology (Clifton, N.J.) · 2025Review
- The Progress in Molecular Transport and Therapeutic Development in Human Blood-Brain Barrier Models in Neurological Disorders.Cellular and molecular neurobiology · 2024Review
- Constitutive knockout of interleukin-6 ameliorates memory deficits and entorhinal astrocytosis in the MRL/lpr mouse model of neuropsychiatric lupus.Journal of neuroinflammation · 2024Article
- Lipocalin-2 drives neuropsychiatric and cutaneous disease in MRL/lpr mice.Frontiers in immunology · 2024Article
- Disease pathology signatures in a mouse model of Mucopolysaccharidosis type IIIB.Scientific reports · 2023Article
- Peripheral inflammatory biomarkers are associated with cognitive function and dementia: Framingham Heart Study Offspring cohort.Aging cell · 2023Article
- Article
- Involvement of TRPM7 in Alcohol-Induced Damage of the Blood-Brain Barrier in the Presence of HIV Viral Proteins.International journal of molecular sciences · 2023Article
- Fn14 and TNFR2 as regulators of cytotoxic TNFR1 signaling.Frontiers in cell and developmental biology · 2023Review
- Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study.Nature communications · 2022Article
- Progress in the Pathogenesis and Treatment of Neuropsychiatric Systemic Lupus Erythematosus.Journal of clinical medicine · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Neuropsychiatric disease is one of the most common manifestations of human systemic lupus erythematosus, but the mechanisms remain poorly understood. In human brain microvascular endothelial cells in vitro, TNF-like weak inducer of apoptosis (TWEAK) decreases tight junction ZO-1 expression and increases the permeability of monolayer cell cultures. Furthermore, knockout (KO) of the TWEAK receptor, Fn14, in the MRL/lpr lupus mouse strain markedly attenuates neuropsychiatric disease, as demonstrated by significant reductions in depressive-like behavior and improved cognitive function. The purpose of the present study was to determine the mechanisms by which TWEAK signaling is instrumental in the pathogenesis of neuropsychiatric lupus (NPSLE). Evaluating brain sections of MRL/lpr Fn14WT and Fn14KO mice, we found that Fn14KO mice displayed significantly decreased cellular infiltrates in the choroid plexus. To evaluate the integrity of the blood brain barrier (BBB) in MRL/lpr mice, Western blot for fibronectin, qPCR for iNOS, and immunohistochemical staining for VCAM-1/ICAM-1 were performed. We found preserved BBB permeability in MRL/lpr Fn14KO mice, attributable to reduced brain expression of VCAM-1/ICAM-1 and iNOS. Additionally, administration of Fc-TWEAK intravenously directly increased the leakage of a tracer (dextran-FITC) into brain tissue. Furthermore, MRL/lpr Fn14KO mice displayed reduced antibody (IgG) and complement (C3, C6, and C4a) deposition in the brain. Finally, we found that MRL/lpr Fn14KO mice manifested reduced neuron degeneration and hippocampal gliosis. Our studies indicate that TWEAK/Fn14 interactions play an important role in the pathogenesis of NPSLE by increasing the accumulation of inflammatory cells in the choroid plexus, disrupting BBB integrity, and increasing neuronal damage, suggesting a novel target for therapy in this disease.
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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.