1,25-dihydroxyvitamin D3-induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells
1,25-dihydroxyvitamin D3-induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells
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1,25-二羟基维生素 D3 诱导的树突状细胞通过增加调节性淋巴细胞的比例并减少 1 型和 17 型辅助 T 细胞来抑制实验性自身免疫性脑脊髓炎。
DOI：
10.1111/imm.12776
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发表时间：
2017-11-01
期刊：
影响因子：
6.4
通讯作者：
Jin, Tao
中科院分区：
文献类型：
--
作者：
Xie, Zhongxiang;Chen, Jingtao;Jin, Tao
树突状细胞(DC)是天然免疫和获得性免疫反应的桥梁，在多发性硬化(MS)和实验性自身免疫性脑脊髓炎(EAE)的发生发展中起着关键作用。维生素D缺乏是MS的环境危险因素。在本研究中，我们用1，25-二羟基维生素D-3诱导耐受树突状细胞，并通过过继转移的方法将耐受树突状细胞(VD3-DC)转移到EAE小鼠体内。我们发现VD3-DC抑制了辅助性T细胞1型(Th1)和Th17细胞向脊髓的渗透，增加了免疫器官中调节性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，从而导致EAE减退。但转移VD3-DC后，小鼠脾和淋巴结中Th1、Th17细胞比例及血清中促炎症细胞因子和免疫球蛋白水平也明显升高。结论：VD3-DC可通过增加脾内调节性T细胞、CD4(+)IL-10(+)T细胞和调节性B细胞的比例，减少Th1、Th17细胞向脊髓的侵袭而抑制EAE，提示VD3-DC治疗MS可能是一种新的免疫治疗方法。
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-3 and transferred the tolerogenic DCs (VD3-DCs) into EAE mice by adoptive transfer. We found that VD3-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 VD3-DCs. We conclude that transfer of VD3-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 VD3-DCs in MS.