Di Liberto, Giovanni and Pantelyushin, Stanislav and Kreutzfeldt, Mario and Page, Nicolas and Musardo, Stefano and Coras, Roland and Steinbach, Karin and Vincenti, Ilene and Klimek, Bogna and Lingner, Thomas and Salinas, Gabriela and Lin-Marq, Nathalie and Staszewski, Ori and Jordao, Marta Joana Costa and Wagner, Ingrid and Egervari, Kristof and Mack, Matthias and Bellone, Camilla and Bluemcke, Ingmar and Prinz, Marco and Pinschewer, Daniel D. and Merkler, Doron (2018) Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping. CELL, 175 (2). 458-+. ISSN 0092-8674, 1097-4172
Full text not available from this repository. (Request a copy)Abstract
Inflammatory disorders of the CNS are frequently accompanied by synaptic loss, 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; MICROGLIA; MICE; CNS; ENCEPHALITIS; COMPLEMENT; ACTIVATION; INTERVENTION; MACROPHAGES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Dec 2019 13:24 |
| Last Modified: | 05 Dec 2019 13:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13708 |
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