Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases.
Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases.
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DOI：
10.1016/j.psyneuen.2009.05.023
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发表时间：
2009-12-01
影响因子：
3.7
通讯作者：
Feron, F
中科院分区：
文献类型：
--
作者：
Fernandes de Abreu, D A;Eyles, D;Feron, F
20多年来，人们已经知道维生素D对免疫细胞和神经细胞有显著的作用。维生素D的这些非经典作用最近引起了人们的重新关注，因为有研究表明，在自身免疫性疾病的动物模型中，维生素D水平的降低会诱发免疫介导的症状，并且是各种脑部疾病的危险因素。例如，已经证明维生素D(1)调节几种神经营养素的产生，(2)上调白细胞介素-4，(3)抑制树突状细胞的分化和存活，导致同种异体反应性T细胞活化受损。不足为奇的是，维生素D已被发现是多发性硬化症（MS）的一个强有力的候选风险调节因素，多发性硬化症是年轻人中最常见的神经和炎症性疾病。维生素D是一种二级类固醇激素，在动物表皮中光化学产生。紫外线（UVB）对7-脱氢胆固醇的作用导致维生素D前体的产生，经过热转化和两次单独的羟基化，产生活性的1,25-二羟基维生素D。维生素D通过两种类型的受体起作用：(i)维生素D受体（VDR），类固醇/甲状腺激素转录因子超家族的成员，（ii） MARRS（膜相关，快速反应类固醇结合）受体，也称为Erp57/Grp58。在这篇文章中，我们回顾了维生素D在各种脑部疾病中可能起作用的一些机制。然后，我们评估维生素D失衡如何为一系列成人疾病奠定基础，包括脑病（帕金森病、癫痫、抑郁症）和免疫介导的疾病（类风湿关节炎、I型糖尿病、系统性红斑狼疮或炎症性肠病）。现在需要多学科的科学合作来充分认识维生素D在哺乳动物代谢中的复杂作用。
It has been known for more than 20 years that vitamin D exerts marked effects on immune and neural cells. These non-classical actions of vitamin D have recently gained a renewed attention since it has been shown that diminished levels of vitamin D induce immune-mediated symptoms in animal models of autoimmune diseases and is a risk factor for various brain diseases. For example, it has been demonstrated that vitamin D (i) modulates the production of several neurotrophins, (ii) up-regulates Interleukin-4 and (iii) inhibits the differentiation and survival of dendritic cells, resulting in impaired allo-reactive T cell activation. Not surprisingly, vitamin D has been found to be a strong candidate risk-modifying factor for Multiple Sclerosis (MS), the most prevalent neurological and inflammatory disease in the young adult population. Vitamin D is a seco-steroid hormone, produced photochemically in the animal epidermis. The action of ultraviolet light (UVB) on 7-dehydrocholesterol results in the production of pre-vitamin D which, after thermo-conversion and two separate hydroxylations, gives rise to the active 1,25-dihydroxyvitamin D. Vitamin D acts through two types of receptors: (i) the vitamin D receptor (VDR), a member of the steroid/thyroid hormone superfamily of transcription factors, and (ii) the MARRS (membrane associated, rapid response steroid binding) receptor, also known as Erp57/Grp58. In this article, we review some of the mechanisms that may underlie the role of vitamin D in various brain diseases. We then assess how vitamin D imbalance may lay the foundation for a range of adult disorders, including brain pathologies (Parkinson's disease, epilepsy, depression) and immune-mediated disorders (rheumatoid arthritis, type I diabetes mellitus, systemic lupus erythematosus or inflammatory bowel diseases). Multidisciplinary scientific collaborations are now required to fully appreciate the complex role of vitamin D in mammal metabolism.