Vitamin D, invariant natural killer T-cells and experimental autoimmune disease.
Vitamin D, invariant natural killer T-cells and experimental autoimmune disease.
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DOI：
10.1017/s0029665111003193
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发表时间：
2012-02
影响因子：
7
通讯作者：
Yang, Linlin
中科院分区：
文献类型：
--
作者：
Cantorna, Margherita T.;Zhao, Jun;Yang, Linlin
维生素 D 是免疫系统的重要调节剂，尤其是多发性硬化症的调节剂。实验 (i) 中，不变的自然杀伤 T (iNKT) 细胞已被证明是自身免疫性疾病的重要抑制因子，例如实验性自身免疫性脑脊髓炎（EAE；多发性硬化症的动物模型）。相反，在实验性过敏性哮喘中，iNKT 细胞是疾病诱导所必需的，因此具有致病性。维生素 D（骨化三醇）的活性形式可抑制 EAE。维生素 D 缺乏会加速 EAE 症状的发展。有趣的是，尽管骨化三醇对疾病严重程度没有影响，但缺乏维生素 D 时实验性哮喘的严重程度较轻。数据表明，维生素 D 在 EAE 和哮喘中的一个重要靶标是 iNKT 细胞。维生素 D 和/或维生素 D 受体缺乏会导致 iNKT 细胞发育受损。维生素 D 在免疫系统发育的早期至关重要。子宫内维生素 D 水平较低，导致 iNKT 细胞数量显着减少，而当使用骨化三醇补充新生或成年小鼠时，这些细胞无法恢复。数据表明，早期维生素 D 缺乏的后果之一是 iNKT 细胞发育数量减少。 iNKT 细胞是骨化三醇在 EAE 中发挥有益作用所必需的。维生素 D 对 iNKT 细胞的重要作用可能会影响人类免疫介导疾病的发展，包括多发性硬化症和哮喘。
Vitamin D is an important regulator of the immune system in general and multiple sclerosis in particular. Experimentally (i), invariant natural killer T (iNKT) cells have been shown to be important suppressors of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE; an animal model of multiple sclerosis). Conversely, in experimental allergic asthma iNKT cells are required for disease induction and are therefore pathogenic. The active form of vitamin D (calcitriol) suppresses EAE. The development of EAE symptoms is accelerated in vitamin D deficiency. Interestingly experimental asthma is less severe in vitamin D deficiency although there is no effect of calcitriol on disease severity. The data suggest that an important target of vitamin D in EAE and asthma are the iNKT cells. Vitamin D and/or vitamin D receptor deficiency results in the impaired development of iNKT cells. Vitamin D is critical very early during development of the immune system. Low levels of vitamin D in utero resulted in significantly reduced numbers of iNKT cells that failed to recover when calcitriol was used to supplement neonatal or adult mice. The data suggest that one of the consequences of early vitamin D deficiency is a reduction in the numbers of iNKT cells that develop. The iNKT cells are required for the beneficial effects of calcitriol in EAE. The important role of vitamin D on iNKT cells could impact the development of human immune-mediated diseases including multiple sclerosis and asthma.