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.

全身性免疫失调有助于神经精神疾病和神经退行性疾病的发展。慢性外周免疫刺激对大脑解剖区域骨髓细胞的确切影响尚不清楚。在这里，我们展示了慢性外周炎症诱导的髓样反应的大脑区域特异性差异。骨髓腔的这种转变与皮质、纹状体和丘脑中炎症性骨髓亚群的出现有关，并伴有区域转录组指纹，包括趋化因子、补体因子和内皮粘附分子的诱导。相比之下，海马和小脑内的骨髓免疫反应是微妙的或不存在的。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区域特异性炎症反应。在类风湿性关节炎患者的死后大脑中观察到区域特异性骨髓细胞对慢性外周炎症的反应。我们的数据表明，慢性外周炎症对大脑具有异质性影响，这一点可以通过在大脑区域观察到的骨髓细胞反应谱来证明。