生物
吞噬细胞
神经科学
小胶质细胞
背景(考古学)
细胞生物学
神经炎症
免疫学
炎症
吞噬作用
古生物学
作者
Giovanni Di Liberto,Stanislav Pantelyushin,Mario Kreutzfeldt,Nicolas Pagé,Stefano Musardo,Roland Coras,Karin Steinbach,Ilena Vincenti,Bogna Klimek,Thomas Lingner,Gabriela Salinas,Nathalie Lin-Marq,Ori Staszewski,Marta Joana Costa Jordão,Ingrid Wagner,Kristóf Égervári,Matthias Mack,Camilla Bellone,Ingmar Blümcke,Marco Prinz,Daniel D. Pinschewer,Doron Merkler
出处
期刊:Cell
[Elsevier]
日期:2018-10-01
卷期号:175 (2): 458-471.e19
被引量:143
标识
DOI:10.1016/j.cell.2018.07.049
摘要
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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