Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease

Neuroinflammation and accumulation of alphα-synuclein (α-syn) are core features of Parkinson disease (PD). We found that α-syn-induced neuroinflammation is driven by antigen presentation from CNS resident macrophages. A subset of these, border-associated macrophages (BAMs), expand and express genes and proteins necessary for immune cell recruitment, infiltration, and antigen presentation, whereas depletion of BAMs prevents neuroinflammation and neurodegeneration. These results point to a critical role for BAMs in initiating PD pathogenesis. Mononuclear cells from 3-4 ventral midbrains pooled per sample, and sorted for CD45+ CD11b+ CX3CR1+ Ly6C- Ly6G- 301 and NK1.1- 302 cells on a BD FACsAria. Sorted cells were loaded onto the 10X Chromium 303 platform (10X genomics), and libraries were constructed using the Single Cell 3′ 304 Reagent Kit V2 according to the manufacturer’s instructions. Two biological replicates for each group were processed separately.

神经炎症与α-突触核蛋白（α-synuclein, α-syn）的聚集是帕金森病（Parkinson Disease, PD）的核心特征。本研究发现，α-突触核蛋白诱导的神经炎症由中枢神经系统（Central Nervous System, CNS）驻留巨噬细胞的抗原呈递所驱动。其中一类亚群——边界相关巨噬细胞（border-associated macrophages, BAMs）——会发生增殖，并表达免疫细胞招募、浸润及抗原呈递所需的基因与蛋白；而清除BAMs则可阻断神经炎症与神经退行性变。上述结果表明，BAMs在帕金森病的发病启动过程中发挥关键作用。每份样本取自3-4个腹侧中脑的单核细胞混合样本，随后通过BD FACSAria流式细胞仪分选得到CD45+ CD11b+ CX3CR1+ Ly6C- Ly6G- 301及NK1.1- 302细胞。分选得到的细胞被接种至10X Chromium 303平台（10X Genomics），并依照制造商说明书，使用单细胞3′ 304试剂试剂盒V2构建测序文库。每组设置两个生物学重复，分别进行独立处理。