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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In the citing paper
“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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Cites
1 retracted
Microglia-dependent synapse loss in type I interferon-mediated lupus
Bialas, A. R., Presumey, J., Das, A., van der Poel, C. E., Lapchak, P. H., Mesin, L., Victora, G., Tsokos, G. C., Mawrin, C., Herbst, R., et al. (2017) · Nature · doi:10.1038/nature22821 · Cited by 197
RetractedR: A Language and Environment for Statistical Computing
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“IFNGR signaling involves the Janus kinases JAK1 and JAK2, which phosphorylate STAT1 and enable its transcription factor activity (Darnell et al., 1994).”
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
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Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · cited 1×
“Of note, complement component C3 is known to play a role in synaptic pruning during postnatal development (Schafer et al., 2012).”
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245
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Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543
The role of inflammation in epilepsy
Vezzani, A., French, J., Bartfai, T., & Baram, T. Z. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.178 · Cited by 1,876
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Salvioni, A. (2018) · theses.fr (ABES) · doi:10.70675/1822c41bzc1afz45a7z8f3dzc8d2bdd4e272
Role of T-cell immunity in the pathophysiology of Alzheimer’s disease and other Tauopathies
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Neuronal STAT1 as a phase switch from antiviral defense to synaptopathy in encephalitis
Liberto, G. D., & Merkler, D. (2026) · Trends in Neurosciences · doi:10.1016/j.tins.2026.04.007
Self-citationvan Loo, K. M. J., Galvis-Montes, D. S., Breuer, A., Berns, J. L., Hummel, C. A., Baumgartner, T. R., Freyberg, M., Mair, K. M., Bauer, J., Rüber, T., et al. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03951-8
Neurons as cytokine sensors in the central nervous system
Kahn, A., Binkle-Ladisch, L., Sonner, J. K., & Friese, M. A. (2026) · Trends in Immunology · doi:10.1016/j.it.2026.07.012 · Cited by 1
Single‐Cell Profiling Reveals Clonally Expanded CX3CR1 + T Cells in Anti‐NMDA Receptor Encephalitis
Yan, L., Zhang, E., Ma, Y., Meng, Z., Li, S., Ren, Y., Tian, X., He, Y., Battaglia, G., Zhou, D., et al. (2026) · Advanced Science · doi:10.1002/advs.77608
Gallus, M., Khan, S. H., Zhao, A., Benway, H., Lu, J., Nejo, T., Watchmaker, P. B., & Okada, H. (2026) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-026-00944-8
Cytokine circuits in CNS homeostasis and disease
Becher, B., Feo, D. D., & Greter, M. (2026) · Nature Immunology · doi:10.1038/s41590-026-02684-3
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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