The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping
Open accessAbstract
Inflammatory disorders of the CNS are frequently accompanied by synaptic loss, which is thought to involve phagocytic microglia and complement components. However, the mechanisms accounting for aberrant synaptic connectivity in the context of CD8+ T cell-driven neuronal damage are poorly understood. Here, we profiled the neuronal translatome in a murine model of encephalitis caused by CD8+ T cells targeting antigenic neurons. Neuronal STAT1 signaling and downstream CCL2 expression were essential for apposition of phagocytes, ensuing synaptic loss and neurological disease. Analogous observations were made in the brains of Rasmussen's encephalitis patients. In this devastating CD8+ T cell-driven autoimmune disease, neuronal STAT1 phosphorylation and CCL2 expression co-clustered with infiltrating CD8+ T cells as well as phagocytes. Taken together, our findings uncover an active role of neurons in coordinating phagocyte-mediated synaptic loss and highlight neuronal STAT1 and CCL2 as critical steps in this process that are amenable to pharmacological interventions.
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“Upon viral infection, endothelial MHC-I presents endogenous viral products and facilitates CD8+ T cell activation (44–46).”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [44]
In the citing paper
“Once activated CD8+ T cells have infiltrated the brain, they can release IFN-γ to stimulate excessive microglial synaptic pruning or inhibit adult neural stem cell proliferation (44, 49), impairing neuronal homeostasis.”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [44]
In the citing paper
“However, work examining the immune response to neurotropic viral infections reveals neuron‐derived inflammatory signaling is a critical feature of the antiviral response (Klein et al, 2005; Chakraborty et al, 2010; Di Liberto et al, 2018).”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Di Liberto et al, 2018
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Metadata
- Authors
- Di Liberto, G., Pantelyushin, S., Kreutzfeldt, M., Page, N., Musardo, S., Coras, R., Steinbach, K., Vincenti, I., Klimek, B., Lingner, T., Salinas, G., Lin-Marq, N., Staszewski, O., Costa Jordão, M. J., Wagner, I., Egervari, K., Mack, M., Bellone, C., Blümcke, I., Prinz, M., Pinschewer, D. D., & Merkler, D.
- Affiliations
- University of Geneva (CH)
- Universitätsklinikum Erlangen (DE)
- Universitätsmedizin Göttingen (DE)
- University Hospital of Geneva (CH)
- University of Freiburg (DE)
- University of Basel (CH)
- Corresponding author
- Merkler, Doron
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 175
- Issue
- 2
- Pages
- 458-471.e19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2888970970
- Cited by
- 195
- References
- 55
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 34 · 2023: 25 · 2022: 34 · 2021: 27 · 2020: 18 · 2019: 19 · 2018: 2
- FWCI
- 7.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- edoc (University of Basel) (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Gebert-Rüf Foundation (GRS-049/13)
- Klaus-Tschira Foundation
- Swiss National Science Foundation
- Swiss MS Society
- Helmut Horten Foundation
- BMBF
- Competence Network of Multiple Sclerosis
- Sobek-Stiftung
- DFG (SFB 992, SFB1160, SFB/TRR167, Reinhart-Koselleck grant)
- Ministry of Science, Research and the Arts, Baden-Wuerttemberg (Sonderlinie “Neuroinflammation”)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- synaptic stripping, CD8+ T cells, MCP-1, microglia, Rasmussen encephalitis, encephalitis, neuroinflammation, autoimmune neurodegeneration
- MeSH terms
- Animals, Brain, Disease Models, Animal, Encephalitis, Female, Humans, Inflammation, Male, Mice, Inbred C57BL, Nervous System Diseases, Neurons, Phagocytes, Phagocytosis, Phosphorylation, Synapses, Microglia, CD8-Positive T-Lymphocytes, Chemokine CCL2, STAT1 Transcription Factor, Mice, Transcriptome
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