ArticleThe EMBO journal2015
USP18 lack in microglia causes destructive interferonopathy of the mouse brain.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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The trial behind it
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Who cites it
138 citing papers in PubMed, 237 citations in OpenAlex.
- Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome.The Journal of experimental medicine · 2016Trial
- Cytokine circuits in CNS homeostasis and disease.Nature immunology · 2026Review
- ISG15 Is a Key Multidirectional Regulator of Cytosolic RNA- and DNA-Sensing Pathways and Type I Interferon Feedback Loops.International journal of molecular sciences · 2026Review
- Role of the miR-340-5p/IRF1/USP18 Axis in Neuroinflammation Associated with Epilepsy.Neurochemical research · 2026Article
- Human ISG15 deficiency unveils impaired healing of ulcerations via type I interferon-mediated fibrosis.Journal of human immunity · 2026Article
- A transcriptomic microglia taxonomy across mouse and human pathologies.Nature immunology · 2026Article
- Impaired TGFβ Signaling in Plaque-Associated Microglia.Biomolecules · 2026Article
- MERS-CoV and SARS-CoV-1 proteins inhibit the IFN-α JAK/STAT pathway of epithelial cells, via IFN-λ-induced USP18.Frontiers in immunology · 2026Article
- Microglial interferon signaling and Aβ plaque pathology are enhanced in female 5xFAD Alzheimer's disease mice, independent of estrous cycle stage.Journal of neuroinflammation · 2025Article
- Ubiquitination in the Nervous System: From Molecular Mechanisms to Disease Implications.Molecular neurobiology · 2025Review
- Interferon-induced protein ISG15 in the central nervous system, quo vadis?FEBS letters · 2025Review
- Regulation of Neuroinflammation by Microglial DUBA-IRAK1-IKKβ Signaling Loop.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Interferon signaling modulates Down syndrome-associated Alzheimer's disease pathology in a mouse model.iScience · 2025Article
- Behavioral assessment and gene expression changes in a mouse model with dysfunctional STAT1 signaling.Cell communication and signaling : CCS · 2025Article
- A Distinguishable Peripheral Blood and Conjunctival Transcriptome and Gut Microbiome in Sjögren's Disease: A Pilot Study.Eye & contact lens · 2025Article
- MSC transplantation ameliorates depression in lupus by suppressing Th1 cell-shaped synaptic stripping.JCI insight · 2025Article
- Review
- Mechanism of USP18-Mediated NCOA4 m6A Modification Via Maintaining FTO Stability In Regulating Ferritinophagy-Mediated Ferroptosis in Cerebral Ischemia-Reperfusion Injury.Molecular neurobiology · 2025Article
- Usp18 Mediates D-Dopachrome Tautomerase-Induced Astrocytic Inflammation After Spinal Cord Injury.Journal of inflammation research · 2025Article
- Targeting USP11 regulation by a novel lithium-organic coordination compound improves neuropathologies and cognitive functions in Alzheimer transgenic mice.EMBO molecular medicine · 2024Article
78 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microglia are tissue macrophages of the central nervous system (CNS) that control tissue homeostasis. Microglia dysregulation is thought to be causal for a group of neuropsychiatric, neurodegenerative and neuroinflammatory diseases, called "microgliopathies". However, how the intracellular stimulation machinery in microglia is controlled is poorly understood. Here, we identified the ubiquitin-specific protease (Usp) 18 in white matter microglia that essentially contributes to microglial quiescence. We further found that microglial Usp18 negatively regulates the activation of Stat1 and concomitant induction of interferon-induced genes, thereby terminating IFN signaling. The Usp18-mediated control was independent from its catalytic activity but instead required the interaction with Ifnar2. Additionally, the absence of Ifnar1 restored microglial activation, indicating a tonic IFN signal which needs to be negatively controlled by Usp18 under non-diseased conditions. These results identify Usp18 as a critical negative regulator of microglia activation and demonstrate a protective role of Usp18 for microglia function by regulating the Ifnar pathway. The findings establish Usp18 as a new molecule preventing destructive microgliopathy.
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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.