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论文题目: Spermidine alleviates experimental autoimmune encephalomyelitis through inducing inhibitory macrophages
英文论文题目: Spermidine alleviates experimental autoimmune encephalomyelitis through inducing inhibitory macrophages
第一作者: Yang, Q; Zheng, C; Cao, J; Cao, G; Shou, P; Lin, L; Velletri, T; Jiang, M; Chen, Q; Han, Y; Li, F; Wang, Y; Cao, W; Shi, Y
英文第一作者: Yang, Q; Zheng, C; Cao, J; Cao, G; Shou, P; Lin, L; Velletri, T; Jiang, M; Chen, Q; Han, Y; Li, F; Wang, Y; Cao, W; Shi, Y
联系作者: Cao, W (reprint author), Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200025, Peoples R China.
英文联系作者: Cao, W (reprint author), Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200025, Peoples R China.
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发表年度: 2016
卷: 23
期: 11
页码: 1850-1861
摘要: Multiple sclerosis (MS) is a chronic and debilitating autoimmune disease, characterized by chronic inflammatory demyelination in the nervous tissue and subsequent neurological dysfunction. Spermidine, a natural polyamine, has been shown to affect inflammation in some experimental models. We show here that spermidine could alleviate experimental autoimmune encephalomyelitis (EAE), a model for MS, through regulating the infiltration of CD4(+) T cells and macrophages in central nervous system. Unexpectedly, we found that spermidine treatment of MOG-specific T cells did not affect their pathogenic potency upon adaptive transfer; however, spermidine diminished the ability of macrophages in activating MOG-specific T cells ex vivo. Depletion of macrophages in diseased mice completely abolished the therapeutic effect of spermidine, indicating a critical role of spermidine-activated macrophages. Mechanistically, spermidine was found to specifically suppress the expression of interleukin-1beta (IL-1 beta), IL-12 and CD80 while enhance the expression of arginase 1 in macrophages. Interestingly, macrophages from spermidine-treated mice could also reverse EAE progression, while pretreatment of those macrophages with the arginase 1 inhibitor abrogated the therapeutic effect. Therefore, our studies revealed a critical role of macrophages in spermidine-mediated treatment on EAE and provided novel information for better management of MS.
英文摘要: Multiple sclerosis (MS) is a chronic and debilitating autoimmune disease, characterized by chronic inflammatory demyelination in the nervous tissue and subsequent neurological dysfunction. Spermidine, a natural polyamine, has been shown to affect inflammation in some experimental models. We show here that spermidine could alleviate experimental autoimmune encephalomyelitis (EAE), a model for MS, through regulating the infiltration of CD4(+) T cells and macrophages in central nervous system. Unexpectedly, we found that spermidine treatment of MOG-specific T cells did not affect their pathogenic potency upon adaptive transfer; however, spermidine diminished the ability of macrophages in activating MOG-specific T cells ex vivo. Depletion of macrophages in diseased mice completely abolished the therapeutic effect of spermidine, indicating a critical role of spermidine-activated macrophages. Mechanistically, spermidine was found to specifically suppress the expression of interleukin-1beta (IL-1 beta), IL-12 and CD80 while enhance the expression of arginase 1 in macrophages. Interestingly, macrophages from spermidine-treated mice could also reverse EAE progression, while pretreatment of those macrophages with the arginase 1 inhibitor abrogated the therapeutic effect. Therefore, our studies revealed a critical role of macrophages in spermidine-mediated treatment on EAE and provided novel information for better management of MS.
刊物名称: CELL DEATH AND DIFFERENTIATION
英文刊物名称: CELL DEATH AND DIFFERENTIATION
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学科: Biochemistry & Molecular Biology; Cell Biology
英文学科: Biochemistry & Molecular Biology; Cell Biology
影响因子: 8.339
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论文类别: Article
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