College of Life Science, Shandong Agricultural University, Taian, 271018, China.
Institute of Immunology, Taishan Medical University, Taian, 271000, China.
Neurosci Bull. 2016 Feb;32(1):70-82. doi: 10.1007/s12264-015-0010-9. Epub 2016 Jan 14.
Microglia are considered to be potential antigen-presenting cells and have the ability to present antigen under pathological conditions. Nevertheless, whether and how microglia are involved in immune regulation are largely unknown. Here, we investigated the suppressive activity of microglia during experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein, with the goal of understanding their role in regulating the T cell reaction. Using flow cytometric analysis, we found that microglia were characterized by increased cell number and up-regulated programmed death ligand-1 (PD-L1) at the peak phase of EAE. Meanwhile, both the CD4(+) T cells and microglia that infiltrated the central nervous system expressed higher levels of PD1, the receptor for PD-L1, accompanied by a decline of Th1 cells. In an ex vivo co-culture system, microglia from EAE mice inhibited the proliferation of antigen-specific CD4(+) T cells and the differentiation of Th1 cells, and this was significantly inhibited by PD-L1 blockade. Further, microglia suppressed Th1 cells via nitric oxide (NO), the production of which was dependent on PD-L1. Thus, these data suggest a scenario in which microglia are involved in the regulation of EAE by suppressing Th1-cell differentiation via the PD-L1-NO pathway.
小胶质细胞被认为是潜在的抗原提呈细胞，在病理条件下具有提呈抗原的能力。然而，小胶质细胞是否以及如何参与免疫调节在很大程度上尚不清楚。在这里，我们研究了小胶质细胞在实验性自身免疫性脑脊髓炎（EAE）中的抑制活性，EAE 由髓鞘少突胶质细胞糖蛋白诱导，目的是了解它们在调节 T 细胞反应中的作用。通过流式细胞术分析，我们发现小胶质细胞在 EAE 的高峰期表现为细胞数量增加和程序性死亡配体-1（PD-L1）上调。同时，浸润中枢神经系统的 CD4(+) T 细胞和小胶质细胞都表达更高水平的 PD1，即 PD-L1 的受体，伴随着 Th1 细胞的减少。在体外共培养系统中，来自 EAE 小鼠的小胶质细胞抑制抗原特异性 CD4(+) T 细胞的增殖和 Th1 细胞的分化，而 PD-L1 阻断显著抑制了这种作用。此外，小胶质细胞通过一氧化氮（NO）抑制 Th1 细胞，其产生依赖于 PD-L1。因此，这些数据表明小胶质细胞通过 PD-L1-NO 途径抑制 Th1 细胞分化参与 EAE 的调节。
