Impact of vitamin D on immune function: lessons learned from genome-wide analysis.
Impact of vitamin D on immune function: lessons learned from genome-wide analysis.
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DOI：
10.3389/fphys.2014.00151
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发表时间：
2014
影响因子：
4
通讯作者：
Hewison M
中科院分区：
文献类型：
--
作者：
Chun RF;Liu PT;Modlin RL;Adams JS;Hewison M
对活性形式维生素D（1，25-二羟基维生素D，1，25 D）的免疫调节反应已被认识多年，但仅在最近5年才认识到其在正常人体免疫功能中的潜在作用。全基因组分析在重新定义我们对维生素D和免疫力的看法方面发挥了关键作用。病原体攻击后巨噬细胞中维生素D受体（VDR）和1α-羟化酶（CYP 27 B1）表达增加的描述强调了胞内分泌维生素D作为先天免疫功能关键介质的重要性。现在很清楚，巨噬细胞和树突状细胞（DC）都能够对25-羟基维生素D（25 D）（主要的循环维生素D代谢物）做出反应，从而提供了这些细胞的功能与许多人常见的维生素D状态变化之间的联系。免疫细胞中数百个主要1，25 D靶基因的鉴定也为维生素D在适应性免疫系统中的作用提供了新的见解，例如抗原呈递和T细胞增殖和表型的调节，其中过度刺激作用是抑制炎症和促进免疫耐受。在巨噬细胞1中，25 D通过诱导抗菌蛋白以及刺激自噬和自噬体活性来促进抗微生物反应。以这种方式，25 D水平的变化有可能影响先天性和适应性免疫应答。最近的全基因组分析强调了细胞因子信号通路如何影响内分泌维生素D系统，并增强或消除对25 D的反应。本综述将讨论内分泌维生素D代谢对先天免疫和适应性免疫的影响，同时介绍疾病特异性维生素D代谢腐败的概念，以及这可能如何改变维持人类健康免疫系统对维生素D的需求。
Immunomodulatory responses to the active form of vitamin D (1,25-dihydroxyvitamin D, 1,25D) have been recognized for many years, but it is only in the last 5 years that the potential role of this in normal human immune function has been recognized. Genome-wide analyses have played a pivotal role in redefining our perspective on vitamin D and immunity. The description of increased vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1) expression in macrophages following a pathogen challenge, has underlined the importance of intracrine vitamin D as key mediator of innate immune function. It is now clear that both macrophages and dendritic cells (DCs) are able to respond to 25-hydroxyvitamin D (25D), the major circulating vitamin D metabolite, thereby providing a link between the function of these cells and the variations in vitamin D status common to many humans. The identification of hundreds of primary 1,25D target genes in immune cells has also provided new insight into the role of vitamin D in the adaptive immune system, such as the modulation of antigen-presentation and T cells proliferation and phenotype, with the over-arching effects being to suppress inflammation and promote immune tolerance. In macrophages 1,25D promotes antimicrobial responses through the induction of antibacterial proteins, and stimulation of autophagy and autophagosome activity. In this way variations in 25D levels have the potential to influence both innate and adaptive immune responses. More recent genome-wide analyses have highlighted how cytokine signaling pathways can influence the intracrine vitamin D system and either enhance or abrogate responses to 25D. The current review will discuss the impact of intracrine vitamin D metabolism on both innate and adaptive immunity, whilst introducing the concept of disease-specific corruption of vitamin D metabolism and how this may alter the requirements for vitamin D in maintaining a healthy immune system in humans.
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DOI：
10.1084/jem.175.4.1111
发表时间：
1992-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan J;Xing Y;Magliozzo RS;Bloom BR
通讯作者：
Bloom BR
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
158.5
作者：
BARBOUR, GL;COBURN, JW;HORST, RL
通讯作者：
HORST, RL
影响因子：
--
作者：
Akutsu, N;Lin, R;White, JH
通讯作者：
White, JH
影响因子：
3.7
作者：
Barlow PG;Svoboda P;Mackellar A;Nash AA;York IA;Pohl J;Davidson DJ;Donis RO
通讯作者：
Donis RO