title: 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.
authors.affiliation: College of Life Science, Shandong Agricultural University, Taian, 271018, China.|Institute of Immunology, Taishan Medical University, Taian, 271000, China.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institute of Immunology, Taishan Medical University, Taian, 271000, China.
authors.forename: Hao
authors.initials: H
authors.lastname: He
authors.affiliation: Department of ENT, Center Hospital of Taian City, Taian, 271000, China.
authors.forename: Zhengang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Taishan Medical University, Taian, 271000, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Institute of Immunology, Taishan Medical University, Taian, 271000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Kang
authors.affiliation: Institute of Immunology, Taishan Medical University, Taian, 271000, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Neurobiology, Jining Medical University, Jining, 272067, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Lu
authors.affiliation: Institute of Immunology, Taishan Medical University, Taian, 271000, China.
authors.forename: Wengang
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Neurobiology, Jining Medical University, Jining, 272067, China. bbai@mail.jnmc.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Bai
authors.affiliation: Institute of Immunology, Taishan Medical University, Taian, 271000, China. tanghuazhang218@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018417:Th1 Cells / Q000166:cytology*
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D009569:Nitric Oxide
keywords: EAE; Microglia; Negative immune regulation; Nitric oxide; PD-L1