Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
Sci Immunol. 2019 Jan 25;4(31). doi: 10.1126/sciimmunol.aau8380.
The central nervous system (CNS) is under close surveillance by immune cells, which mediate tissue homeostasis, protection, and repair. Conversely, in neuroinflammation, dysregulated leukocyte invasion into the CNS leads to immunopathology and neurological disability. To invade the brain parenchyma, autoimmune encephalitogenic T helper (T) cells must encounter their cognate antigens (Ags) presented via local Ag-presenting cells (APCs). The precise identity of the APC that samples, processes, and presents CNS-derived Ags to autoaggressive T cells is unknown. Here, we used a combination of high-dimensional single-cell mapping and conditional MHC class II ablation across all CNS APCs to systematically interrogate each population for its ability to reactivate encephalitogenic T cells in vivo. We found a population of conventional dendritic cells, but not border-associated macrophages or microglia, to be essential for licensing T cells to initiate neuroinflammation.
中枢神经系统（CNS）受到免疫细胞的严密监视，这些免疫细胞介导组织稳态、保护和修复。相反，在神经炎症中，白细胞失调地侵入中枢神经系统会导致免疫病理学和神经功能障碍。为了侵入脑组织，自身免疫性脑炎反应性辅助性 T 细胞（T 细胞）必须遇到通过局部抗原呈递细胞（APC）呈递的其同源抗原（Ags）。负责摄取、处理和向自身反应性 T 细胞呈递中枢神经系统源性 Ag 的 APC 的确切身份尚不清楚。在这里，我们使用了高维单细胞图谱绘制技术，并对所有中枢神经系统 APC 进行了 MHC II 类条件性基因敲除，以系统地研究每个细胞群在体内重新激活致脑炎 T 细胞的能力。我们发现，传统树突状细胞群，而不是边缘相关的巨噬细胞或小胶质细胞，对于许可 T 细胞引发神经炎症是必不可少的。
