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

Abstract

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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81070961, 81273212, 81202308, 81302604, 31300730, 81172882, and 81241052) and the Natural Science Foundation of Shandong Province (ZR2011CM037). We thank Qiuling Zhang for assistance with the maintenance of mice; and Yalin Li and Yingping Xu for critical reading of the manuscript.

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Correspondence to Bo Bai or Hua Tang.

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Jingxia Hu and Hao He have contributed equally to this work.

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Hu, J., He, H., Yang, Z. et al. Programmed Death Ligand-1 on Microglia Regulates Th1 Differentiation via Nitric Oxide in Experimental Autoimmune Encephalomyelitis. Neurosci. Bull. 32, 70–82 (2016). https://doi.org/10.1007/s12264-015-0010-9

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Keywords

  • Microglia
  • Negative immune regulation
  • PD-L1
  • Nitric oxide
  • EAE