Department of Molecular Neurology, Friedrich Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91054 Erlangen, Germany; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, 79106 Freiburg im Breisgau, Germany.
Department of Molecular Neurology, Friedrich Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91054 Erlangen, Germany.
Cell Rep. 2020 Mar 24;30(12):4082-4095.e6. doi: 10.1016/j.celrep.2020.02.109.
Systemic immune dysregulation contributes to the development of neuropsychiatric and neurodegenerative diseases. The precise effect of chronic peripheral immune stimulation on myeloid cells across anatomical brain regions is unclear. Here, we demonstrate brain-region-specific differences in myeloid responses induced by chronic peripheral inflammation. This shift in the myeloid compartment is associated with the appearance of an inflammatory myeloid subpopulation in the cortex, striatum, and thalamus accompanied by regional transcriptomic fingerprints that include induction of chemokines, complement factors, and endothelial adhesion molecules. In contrast, myeloid immune responses within the hippocampus and cerebellum are subtle or absent. Treatment with the anti-tumor necrosis factor α (anti-TNF-α) antibody infliximab ablates the region-specific inflammatory response. A region-specific myeloid cell response to chronic peripheral inflammation is observed in postmortem brains from individuals with rheumatoid arthritis. Our data suggest that chronic peripheral inflammation has heterogeneous effects on the brain, as evidenced by the spectrum of myeloid cell responses observed across brain regions.
系统性免疫失调导致神经精神和神经退行性疾病的发生。慢性外周免疫刺激对解剖脑区的髓样细胞的确切影响尚不清楚。在这里，我们证明了慢性外周炎症诱导的髓样细胞反应存在脑区特异性差异。这种髓样细胞区室的转变与皮质、纹状体和丘脑中炎症性髓样细胞亚群的出现有关，伴有趋化因子、补体因子和内皮细胞黏附分子的诱导等区域转录组特征。相比之下，海马体和小脑的髓样免疫反应则较为轻微或不存在。使用抗肿瘤坏死因子 α（抗 TNF-α）抗体英夫利昔单抗治疗可消除这种区域特异性炎症反应。在类风湿关节炎患者的死后大脑中也观察到了对慢性外周炎症的区域特异性髓样细胞反应。我们的数据表明，慢性外周炎症对大脑有不同的影响，这可以从观察到的跨脑区髓样细胞反应的范围得到证明。
