ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
The type I interferon-alpha mediates a more severe neurological disease in the absence of the canonical signaling molecule interferon regulatory factor 9.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Altered increase in STAT1 expression and phosphorylation in severe COVID-19.European journal of immunology · 2022Trial
- Antiviral innate immunity induces alpha synuclein phosphorylation at serine129 in neurons independent of aggregation.NPJ Parkinson's disease · 2026Article
- Interleukin-6-induced neuroinflammation is exacerbated by subclinical levels of interferon-α.Frontiers in neuroscience · 2025Article
- The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench.Immunological reviews · 2024Review
- Extracellular Vesicles: The Invisible Heroes and Villains of COVID-19 Central Neuropathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- 'Spikeopathy': COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA.Biomedicines · 2023Review
- Long non-coding RNA TTTY15 sponges miR-520a-3p to exacerbate neural apoptosis induced by cerebral ischemia/reperfusion via targeting IRF9 both in vivo and in vitro.Biomedical journal · 2023Article
- Roles and mechanisms of exosomal microRNAs in viral infections.Archives of virology · 2023Review
- Breaking down the cellular responses to type I interferon neurotoxicity in the brain.Frontiers in immunology · 2023Review
- Circulating microRNAs as emerging regulators of COVID-19.Theranostics · 2023Review
- Post-COVID-19 Parkinsonism and Parkinson's Disease Pathogenesis: The Exosomal Cargo Hypothesis.International journal of molecular sciences · 2022Review
- Differential Retinal Ganglion Cell Vulnerability, A Critical Clue for the Identification of Neuroprotective Genes in Glaucoma.Frontiers in ophthalmology · 2022Review
- SARS-CoV-2 Spike Targets USP33-IRF9 AxisFrontiers in immunology · 2021Article
- Porcine Reproductive and Respiratory Syndrome Virus nsp11 Antagonizes Type I Interferon Signaling by Targeting IRF9.Journal of virology · 2019Article
- IRF9 Prevents CD8Journal of virology · 2017Article
- Type I interferon-regulated gene expression and signaling in murine mixed glial cells lacking signal transducers and activators of transcription 1 or 2 or interferon regulatory factor 9.The Journal of biological chemistry · 2017Article
- Article
- Human TBK1: A Gatekeeper of Neuroinflammation.Trends in molecular medicine · 2016Review
- Gene-Expression Profiling Suggests Impaired Signaling via the Interferon Pathway in Cstb-/- Microglia.PloS one · 2016Article
- A critical role for interferon regulatory factor 9 in cerebral ischemic stroke.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type I interferons (IFN) are crucial in host defense but also are implicated as causative factors for neurological disease. Interferon regulatory factor (IRF9) is involved in type I IFN-regulated gene expression where it associates with STAT1:STAT2 heterodimers to form the transcriptional complex ISGF3. The role of IRF9 in cellular responses to type I IFN is poorly defined in vivo and hence was examined here. While transgenic mice (termed GIFN) with chronic production of low levels of IFN-alpha in the CNS were relatively unaffected, the same animals lacking IRF9 [GIFNxIRF9 knock-out (KO)] had cataracts, became moribund, and died prematurely. The brain of GIFNxIRF9 KO mice showed calcification with pronounced inflammation and neurodegeneration whereas inflammation and retinal degeneration affected the eyes. In addition, IFN-gamma-like gene expression in the CNS in association with IFN-gamma mRNA and increased phosphotyrosine-STAT1 suggested a role for IFN-gamma. However, GIFNxIRF9 KO mice deficient for IFN-gamma signaling developed an even more severe and accelerated disease, indicating that IFN-gamma was protective. In IRF9-deficient cultured mixed glial cells, IFN-alpha induced prolonged activation of STAT1 and STAT2 and induced the expression of IFN-gamma-like genes. We conclude that (1) type I IFN signaling and cellular responses can occur in vivo in the absence of IRF9, (2) IRF9 protects against the pathophysiological actions of type I IFN in the CNS, and (3) STAT1 and possibly STAT2 participate in alternative IRF9-independent signaling pathways activated by IFN-alpha in glial cells resulting in enhanced IFN-gamma-like responses.
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Registered trials
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