Oral Administration of an Active Form of Vitamin D3 (Calcitriol) Decreases Atherosclerosis in Mice by Inducing Regulatory T Cells and Immature Dendritic Cells With Tolerogenic Functions
Oral Administration of an Active Form of Vitamin D3 (Calcitriol) Decreases Atherosclerosis in Mice by Inducing Regulatory T Cells and Immature Dendritic Cells With Tolerogenic Functions
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DOI：
10.1161/atvbaha.110.215459
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发表时间：
2010-12-01
影响因子：
8.7
通讯作者：
Hirata, Ken-ichi
中科院分区：
文献类型：
--
作者：
Takeda, Masafumi;Yamashita, Tomoya;Hirata, Ken-ichi
为了确定是否管理的活性形式的维生素D-3（骨化三醇）可以防止动脉粥样硬化通过抗炎actions.Methods和结果最近的临床研究表明，缺乏维生素D-3是心血管事件的危险因素。与对照小鼠的相应观察结果相比，口服骨化三醇可减少动脉粥样硬化病变、巨噬细胞积聚和主动脉窦处的CD 4（+）T细胞浸润。我们观察到口服骨化三醇的小鼠肠系膜淋巴结、脾脏和动脉粥样硬化病变中Foxp 3（+）调节性T细胞显著增加，CD 80（+）CD 86（+）树突状细胞（DC）减少，这与白细胞介素10 mRNA表达增加和白细胞介素12 mRNA表达减少有关。骨化三醇组的CD 11 c（+）DC显示T淋巴细胞增殖活性降低，表明DC成熟受到抑制。CD 25在体内的中和作用表明，骨化三醇抑制动脉粥样硬化主要是在调节性T细胞依赖的方式，但也部分是因为减少在DC的成熟。结论口服骨化三醇治疗可以通过改变功能或分化的DC和调节性T细胞，防止动脉粥样硬化的发展。这些研究结果表明，肠道和全身免疫调节骨化三醇可能是一个潜在的有价值的治疗方法对动脉粥样硬化。（Arterioscler Thromb Vasc Biol.2010;30：2495-2503.）
Objective-To determine whether the administration of an active form of vitamin D-3 (calcitriol) could prevent atherosclerosis through anti-inflammatory actions.Methods and Results-Recent clinical studies have shown that lack of vitamin D-3 is a risk factor for cardiovascular events. Oral calcitriol administration decreased atherosclerotic lesions, macrophage accumulation, and CD4(+) T-cell infiltration at the aortic sinus, when compared with the corresponding observations in control mice. We observed a significant increase in Foxp3(+) regulatory T cells and a decrease in CD80(+) CD86(+) dendritic cells (DCs) in the mesenteric lymph nodes, spleen, and atherosclerotic lesions in oral calcitriol-treated mice in association with increased interleukin 10 and decreased interleukin 12 mRNA expression. CD11c(+) DCs from the calcitriol group showed reduced proliferative activity of T lymphocytes, suggesting the suppression of DC maturation. Neutralization of CD25 in vivo revealed that calcitriol inhibited atherosclerosis mainly in a regulatory T cell-dependent manner but also partly because of a decrease in DC maturation.Conclusion-Oral calcitriol treatment could prevent the development of atherosclerosis by changing the function or differentiation of DCs and regulatory T cells. These findings suggest that intestinal and systemic immune modulation by calcitriol may be a potentially valuable therapeutic approach against atherosclerosis. (Arterioscler Thromb Vasc Biol. 2010;30:2495-2503.)