ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Absence of IFN-γ increases brain pathology in experimental autoimmune encephalomyelitis-susceptible DRB1*0301.DQ8 HLA transgenic mice through secretion of proinflammatory cytokine IL-17 and induction of pathogenic monocytes/microglia into the central nervous system.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- IL-17A deficiency in HLA-DR3 transgenic mice enriches beneficial Prevotella species in gut to promote Tregs and reduce CNS autoimmunity.Microbiome · 2026Article
- Integrating Genomic, eQTL, and Mendelian Randomization Analyses to Identify Microglial Drug Targets in Multiple Sclerosis.Journal of cellular and molecular medicine · 2025Article
- Mac-1 regulates disease stage-specific immunosuppression via the nitric oxide pathway in autoimmune disease.Science advances · 2025Article
- Review
- The Mechanisms of Altered Blood-Brain Barrier Permeability in CD19 CAR T-Cell Recipients.International journal of molecular sciences · 2024Review
- Concurrent Brain Subregion Microgliosis in an HLA-II Mouse Model of Group A Streptococcal Skin Infection.Microorganisms · 2023Article
- Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice.BMC microbiology · 2022Article
- Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis.Science advances · 2021Article
- Interferon-γ Involvement in the Neuroinflammation Associated with Parkinson's Disease and L-DOPA-Induced Dyskinesia.Neurotoxicity research · 2021Article
- Altered Cytokine Endotoxin Responses in Neonatal Encephalopathy Predict MRI Outcomes.Frontiers in pediatrics · 2021Article
- GM-CSF induces noninflammatory proliferation of microglia and disturbs electrical neuronal network rhythms in situ.Journal of neuroinflammation · 2020Article
- Albendazole-Schisandrin B Co-Therapy onBiomolecules · 2020Article
- The Role of Granulocyte-Macrophage Colony-Stimulating Factor in Murine Models of Multiple Sclerosis.Cells · 2020Review
- Human CommensalFrontiers in immunology · 2020Article
- Hemp seed/evening primrose oil affects expression of STAT3, IL-17, and FOXP3Research in pharmaceutical sciences · 2019Article
- Regulatory effects of hemp seed/evening primrose oil supplement in comparison with rapamycin on the expression of the mammalian target ofResearch in pharmaceutical sciences · 2019Article
- Article
- The potential effects of hemp seed/evening primrose oils on the mammalian target of rapamycin complex 1 and interferon-gamma genes expression in experimental autoimmune encephalomyelitis.Research in pharmaceutical sciences · 2018Article
- α-Synuclein activates innate immunity but suppresses interferon-γ expression in murine astrocytes.The European journal of neuroscience · 2018Article
- GM-CSF is not essential for experimental autoimmune encephalomyelitis but promotes brain-targeted disease.JCI insight · 2017Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Multiple sclerosis is an inflammatory, demyelinating disease of the CNS of presumed autoimmune origin. Of all the genetic factors linked with multiple sclerosis, MHC class II molecules have the strongest association. Generation of HLA class II transgenic (Tg) mice has helped to elucidate the role of HLA class II genes in chronic inflammatory and demyelinating diseases. We have shown that the human HLA-DRB1*0301 gene predisposes to proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE), whereas HLA-DQβ1*0601 (DQ6) was resistant. We also showed that the DQ6 molecule protects from EAE in DRB1*0301.DQ6 double-Tg mice by producing anti-inflammatory IFN-γ. HLA-DQβ1*0302 (DQ8) Tg mice were also resistant to PLP(91-110)-induced EAE, but production of proinflammatory IL-17 exacerbated disease in DRB1*0301.DQ8 mice. To further confirm the role of IFN-γ in protection, we generated DRB1*0301.DQ8 mice lacking IFN-γ (DRB1*0301.DQ8.IFN-γ(-/-)). Immunization with PLP(91-110) peptide caused atypical EAE in DRB1*0301.DQ8.IFN-γ(-/-) mice characterized by ataxia, spasticity, and dystonia, hallmarks of brain-specific disease. Severe brain-specific inflammation and demyelination in DRB1*0301.DQ8.IFN-γ(-/-) mice with minimal spinal cord pathology further confirmed brain-specific pathology. Atypical EAE in DRB1*0301.DQ8.IFN-γ(-/-) mice was associated with increased encephalitogenicity of CD4 T cells and their ability to produce greater levels of IL-17 and GM-CSF compared with DRB1*0301.DQ8 mice. Further, areas with demyelination showed increased presence of CD68(+) inflammatory cells, suggesting an important role for monocytes/microglia in causing brain pathology. Thus, our study supports a protective role for IFN-γ in the demyelination of brain through downregulation of IL-17/GM-CSF and induction of neuroprotective factors in the brain by monocytes/microglial cells.
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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.