Programmed Death Ligand-1 on Microglia Regulates Th1 Differentiation via Nitric Oxide in Experimental Autoimmune Encephalomyelitis
Programmed Death Ligand-1 on Microglia Regulates Th1 Differentiation via Nitric Oxide in Experimental Autoimmune Encephalomyelitis
复制标题
小胶质细胞上的程序性死亡配体-1 通过一氧化氮调节实验性自身免疫性脑脊髓炎中的 Th1 分化
DOI：
10.1007/s12264-015-0010-9
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发表时间：
2016-02-01
影响因子：
5.6
通讯作者：
Tang, Hua
中科院分区：
文献类型：
--
作者：
Hu, Jingxia;He, Hao;Tang, Hua
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是未知的。在此，我们研究了在髓鞘少突胶质细胞糖蛋白诱导的实验性自身免疫性脑脊髓炎(EAE)过程中小胶质细胞的抑制活性，目的是了解它们在调节T细胞反应中的作用。流式细胞仪分析发现，在EAE的高峰期，小胶质细胞的特征是细胞数量增加，程序性死亡配体-1(PD-L1)表达上调。同时，渗入中枢神经系统的CD4(+)T细胞和小胶质细胞均表达较高水平的PD-L1受体，并伴有Th1细胞的下降。在体外共培养系统中，EAE小鼠的小胶质细胞抑制抗原特异性的CD4(+)T细胞的增殖和Th1细胞的分化，这一作用可被PD-L1阻断显著抑制。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。
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.