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1,25-二羟基维生素D诱导的树突状细胞通过增加调节性淋巴细胞比例并减少1型和17型辅助性T细胞来抑制实验性自身免疫性脑脊髓炎。

1,25-dihydroxyvitamin D -induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells.

作者信息

Xie Zhongxiang, Chen Jingtao, Zheng Chao, Wu Jing, Cheng Yun, Zhu Shan, Lin Chenhong, Cao Qingqing, Zhu Jie, Jin Tao

机构信息

Department of Neurology and Neuroscience Centre, The First Hospital of Jilin University, Changchun, China.

Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.

出版信息

Immunology. 2017 Nov;152(3):414-424. doi: 10.1111/imm.12776. Epub 2017 Jul 10.

Abstract

Dendritic cells (DCs), a bridge for innate and adaptive immune responses, play a key role in the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Administration of tolerogenic DCs has been used as an immunotherapy in autoimmune diseases. Deficiency of vitamin D is an environmental risk factor of MS. In this study, we induced tolerogenic DCs by 1,25-dihydroxyvitamin D and transferred the tolerogenic DCs (VD -DCs) into EAE mice by adoptive transfer. We found that VD -DCs inhibited the infiltrations of T helper type 1 (Th1) and Th17 cells into spinal cord and increased the proportions of regulatory T cells (CD4 CD25 Foxp3 ), CD4 IL-10 T cells and regulatory B cells (CD19 CD5 CD1d ) in peripheral immune organs, which resulted in attenuated EAE. However, the proportions of T helper type 1 (Th1) and Th17 cells in spleen and lymph nodes and the levels of pro-inflammatory cytokines and IgG in serum also increased after transfer of VD -DCs. We conclude that transfer of VD -DCs suppressed EAE by increasing proportions of regulatory T cells, CD4 IL-10 T cells and regulatory B cells in spleen and reducing infiltration of Th1 and Th17 cells into spinal cord, which suggests a possible immunotherapy method using VD -DCs in MS.

摘要

树突状细胞(DCs)是先天性免疫反应和适应性免疫反应之间的桥梁,在多发性硬化症(MS)及其实验性自身免疫性脑脊髓炎(EAE,MS的动物模型)的发病过程中发挥关键作用。给予耐受性DCs已被用作自身免疫性疾病的一种免疫疗法。维生素D缺乏是MS的一个环境风险因素。在本研究中,我们用1,25-二羟基维生素D诱导产生耐受性DCs,并通过过继转移将耐受性DCs(VD-DCs)转入EAE小鼠体内。我们发现,VD-DCs抑制了1型辅助性T细胞(Th1)和Th17细胞向脊髓的浸润,并增加了外周免疫器官中调节性T细胞(CD4⁺CD25⁺Foxp3⁺)、CD4⁺IL-10⁺T细胞和调节性B细胞(CD19⁺CD5⁺CD1d⁺)的比例,从而减轻了EAE。然而,VD-DCs转移后,脾脏和淋巴结中Th1和Th17细胞的比例以及血清中促炎细胞因子和IgG的水平也有所增加。我们得出结论,VD-DCs的转移通过增加脾脏中调节性T细胞、CD4⁺IL-10⁺T细胞和调节性B细胞的比例以及减少Th1和Th17细胞向脊髓的浸润来抑制EAE,这提示了一种在MS中使用VD-DCs的可能的免疫治疗方法。

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本文引用的文献

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Circulating immune cells in multiple sclerosis.多发性硬化症中的循环免疫细胞。
Clin Exp Immunol. 2017 Feb;187(2):193-203. doi: 10.1111/cei.12878. Epub 2016 Nov 2.

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