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CD4+T cell specific B7-H1 selectively inhibits proliferation of naive T cells and Th17 differentiation in experimental autoimmune encephalomyelitis.

ABSTRACT: It is widely acknowledged that interleukin 17-producing T helper (Th17) cells are critically participant in the pathogenesis of multiple sclerosis. In the current study, we identified that the expression of CD4+T cells specific co-inhibitory molecule B7-homologue 1(B7-H1) in spleenocytes and mononuclear cells isolated from brains and spinal cord were positive correlated with Th1 and Th17 cells generation and disease severity in experimental autoimmune encephalomyelitis (EAE). Furthermore, B7-H1 transgenic mice developed milder EAE symptoms and fewer Th17 cells than B7-H1 wild type mice. We also found the proliferation of naïve CD4+CD62+T cells isolated from B7-H1 transgenic mice was inhibited. And naïve T cells isolated from B7-H1 transgenic mice produced fewer Th17 cells than WT mice in Th17-polarizing conditions, but the Th1, Th2, and inducible Treg differentiation were the similar in naïve T cells isolated from B7-H1 transgenic mice and WT mice. In conclusion, our study show CD4+T cells specific B7-H1 is a slective inhibitor in proliferation of naïve T cells, Th17 differentiation and pathogenesis of multiple sclerosis.

SUBMITTER: Shi SJ

PROVIDER: S-EPMC5685729 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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CD4<sup>+</sup>T cell specific B7-H1 selectively inhibits proliferation of naïve T cells and Th17 differentiation in experimental autoimmune encephalomyelitis.

Shi Sheng-Jia SJ Ding Mei-Ling ML Wang Li-Juan LJ Wu Jie-Heng JH Han Dong-Hui DH Zheng Guo-Xu GX Guo Zhang-Yan ZY Xi Wen-Jin WJ Qin Wei-Jun WJ Yang An-Gang AG Wen Wei-Hong WH

Oncotarget 20170928 52

It is widely acknowledged that interleukin 17-producing T helper (Th17) cells are critically participant in the pathogenesis of multiple sclerosis. In the current study, we identified that the expression of CD4<sup>+</sup>T cells specific co-inhibitory molecule B7-homologue 1(B7-H1) in spleenocytes and mononuclear cells isolated from brains and spinal cord were positive correlated with Th1 and Th17 cells generation and disease severity in experimental autoimmune encephalomyelitis (EAE). Furtherm ...[more]

PMID: 29163808

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Project description:BackgroundMultiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by severe white matter demyelination. Because of its complex pathogenesis, there is no definite cure for MS. Experimental autoimmune encephalomyelitis (EAE) is an ideal animal model for the study of MS. Arsenic trioxide (ATO) is an ancient Chinese medicine used for its therapeutic properties with several autoimmune diseases. It is also used to inhibit acute immune rejection due to its anti-inflammatory and immunosuppressive properties. However, it is unclear whether ATO has a therapeutic effect on EAE, and the underlying mechanisms have not yet been clearly elucidated. In this study, we attempted to assess whether ATO could be used to ameliorate EAE in mice.MethodsATO (0.5 mg/kg/day) was administered intraperitoneally to EAE mice 10 days post-immunization for 8 days. On day 22 post-immunization, the spinal cord, spleen, and blood were collected to analyze demyelination, inflammation, microglia activation, and the proportion of CD4+ T cells. In vitro, for mechanistic studies, CD4+ T cells were sorted from the spleen of naïve C57BL/6 mice and treated with ATO and then used for an apoptosis assay, JC-1 staining, imaging under a transmission electron microscope, and western blotting.ResultsATO delayed the onset of EAE and alleviated the severity of EAE in mice. Treatment with ATO also attenuated demyelination, alleviated inflammation, reduced microglia activation, and decreased the expression levels of IL-2, IFN-γ, IL-1β, IL-6, and TNF-α in EAE mice. Moreover, the number and proportion of CD4+ T cells in the spinal cord, spleen, and peripheral blood were reduced in ATO-treated EAE mice. Finally, ATO induced CD4+ T cell apoptosis via the mitochondrial pathway both in vitro and in vivo. Additionally, the administration of ATO had no adverse effect on the heart, liver, or kidney function, nor did it induce apoptosis in the spinal cord.ConclusionsOverall, our findings indicated that ATO plays a protective role in the initiation and progression of EAE and has the potential to be a novel drug in the treatment of MS.

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CD4+T cell specific B7-H1 selectively inhibits proliferation of naive T cells and Th17 differentiation in experimental autoimmune encephalomyelitis.

Publications

CD4<sup>+</sup>T cell specific B7-H1 selectively inhibits proliferation of naïve T cells and Th17 differentiation in experimental autoimmune encephalomyelitis.

Similar Datasets

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