ArticleJournal of neuroinflammation2020
The impact of regional astrocyte interferon-γ signaling during chronic autoimmunity: a novel role for the immunoproteasome.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Astrocytes in Multiple Sclerosis: Getting to the Core.International journal of molecular sciences · 2026Review
- The rise of astrocytes: are they guardians or troublemakers of the brain disorder?Experimental & molecular medicine · 2026Review
- Context matters: Conflicting roles of interferon-γ signaling in CNS diseases.Current opinion in neurobiology · 2026Review
- T cell-mediated immunodysregulation in multiple sclerosis: from pathogenic subsets to therapeutic advances.Frontiers in immunology · 2026Review
- Spatial protein profiling reveals active roles for astrocytes in the chronic active lesion core during multiple sclerosis.Acta neuropathologica · 2025Article
- BATF2 is a regulator of interferon-γ signaling in astrocytes during neuroinflammation.Cell reports · 2025Article
- Exploring neuroglial signaling: diversity of molecules implicated in microglia-to-astrocyte neuroimmune communication.Reviews in the neurosciences · 2025Review
- Astrocytes in aging.Neuron · 2025Review
- Astrocytic BDNF Modulates Sensitivity to Stress-Induced Anxiety-Like Behaviors.Research (Washington, D.C.) · 2025Article
- Targeting the immunoproteasome in hypothalamic neurons as a novel therapeutic strategy for high-fat diet-induced obesity and metabolic dysregulation.Journal of neuroinflammation · 2024Article
- Orchestrating Stress Responses in Multiple Sclerosis: A Role for Astrocytic IFNγ Signaling.International journal of molecular sciences · 2024Review
- Review
- A novelFrontiers in cellular neuroscience · 2024Article
- Astrocyte interferon-gamma signaling dampens inflammation during chronic central nervous system autoimmunity via PD-L1.Journal of neuroinflammation · 2023Article
- Prolonged STAT1 activation in neurons drives a pathological transcriptional response.Journal of neuroimmunology · 2023Article
- PD-L1 positive astrocytes attenuate inflammatory functions of PD-1 positive microglia in models of autoimmune neuroinflammation.Nature communications · 2023Article
- The immunology of multiple sclerosis.Nature reviews. Immunology · 2022Review
- Interferon-gamma and neuropathy: balance between pain and neuroprotection.Neural regeneration research · 2022Article
- Exogenous Antioxidants in Remyelination and Skeletal Muscle Recovery.Biomedicines · 2022Review
- Targetability of the neurovascular unit in inflammatory diseases of the central nervous system.Immunological reviews · 2022Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIn early autoimmune neuroinflammation, interferon (IFN)γ and its upregulation of the immunoproteasome (iP) is pathologic. However, during chronic multiple sclerosis (MS), IFNγ has protective properties. Although dysregulation of the iP has been implicated in neurodegeneration, its function remains to be fully elucidated. Here, we demonstrate that IFNγ signaling in regional astrocytes induces the iP and promotes protection of the CNS during chronic autoimmunity.
methodsIn a multiple sclerosis (MS) brain, we evaluated mRNA expression and labeled postmortem MS brainstem and spinal cord for iP subunits and indicators of oxidative stress. Primary regional human astrocytes were analyzed for iP regulation and function by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, OxyBlot, and reactive oxygen species and caspase activity detection assays. Following immunization with myelin oligodendrocyte glycoprotein (MOG)
resultsIn MS tissue, iP expression was enhanced in the spinal cord compared to brainstem lesions, which correlated with a decrease in oxidative stress. In vitro, IFNγ stimulation enhanced iP expression, reduced reactive oxygen species burden, and decreased oxidatively damaged and poly-ubiquitinated protein accumulation preferentially in human spinal cord astrocytes, which was abrogated with the use of the iP inhibitor, ONX 0914. During the chronic phase of an MS animal model, EAE, ONX 0914 treatment exacerbated the disease and led to increased oxidative stress and poly-ubiquitinated protein buildup. Finally, mice with astrocyte-specific loss of the IFNγ receptor exhibited worsened chronic EAE associated with reduced iP expression, enhanced lesion size and oxidative stress, and poly-ubiquitinated protein accumulation in astrocytes.
conclusionsTaken together, our data reveal a protective role for IFNγ in chronic neuroinflammation and identify a novel function of the iP in astrocytes during CNS autoimmunity.
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