Programmed Death Ligand-1 on Microglia Regulates Th1 Differentiation via Nitric Oxide in Experimental Autoimmune Encephalomyelitis

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• 作者：Jingxia Hu ; Hao He ; Zhengang Yang ; Guangming Zhu ; Li Kang…
• 关键词：Microglia ; Negative immune regulation ; PD ; L1 ; Nitric oxide ; EAE
• 刊名：Neuroscience Bulletin
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：32
• 期：1
• 页码：70-82
• 全文大小：3,199 KB
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• 作者单位：Jingxia Hu (1) (2)
  Hao He (2)
  Zhengang Yang (3)
  Guangming Zhu (2)
  Li Kang (2)
  Xiuli Jing (2)
  Hai Lu (4)
  Wengang Song (2)
  Bo Bai (4)
  Hua Tang (2)
  
  1. College of Life Science, Shandong Agricultural University, Taian, 271018, China
  2. Institute of Immunology, Taishan Medical University, Taian, 271000, China
  3. Department of ENT, Center Hospital of Taian City, Taian, 271000, China
  4. Department of Neurobiology, Jining Medical University, Jining, 272067, China
  
• 刊物主题：Neurosciences; Human Physiology; Anesthesiology; Anatomy; Neurology; Pain Medicine;
• 出版者：Springer Berlin Heidelberg
• ISSN：1995-8218

文摘

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. Keywords Microglia Negative immune regulation PD-L1 Nitric oxide EAE