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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From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Di Liberto et al, 2018
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- 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 › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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