Vitamin D and the intracrinology of innate immunity.

Vitamin D and the intracrinology of innate immunity.
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DOI:
10.1016/j.mce.2010.02.013
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发表时间:
2010-06-10
影响因子:
4.1
通讯作者:
Hewison M
Hewison M
中科院分区:
医学2区
文献类型:
--
作者:
Hewison M

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维生素D的免疫调节作用在25年前首次提出,基于两个显著的观察结果。首先,研究表明肉芽肿性结节病患者的单核/巨噬细胞组成性地从前体25-羟基维生素D (25OHD)合成活性形式的维生素D 1,25-二羟基维生素D (1,25(OH)2D)。其次,在活化的增殖淋巴细胞中可以检测到125 (OH)2D(维生素D受体,VDR)的受体。这些观察结果表明,单核细胞产生的1,25(OH)2D可以作用于邻近的t细胞或b细胞,但这种系统对正常免疫调节的影响尚不确定。事实上,直到最近几年,人们才对维生素D作为免疫反应性决定因素的作用有了更清晰的认识。两个新概念促使了这种变化。首先,先天免疫研究表明,维生素D在细胞内诱导抗菌活性是单核/巨噬细胞对感染反应的关键组成部分。其次,现在很清楚,维生素D状态不佳是世界上许多人群的共同特征,有可能损害单核细胞/巨噬细胞对25OHD的代谢和随后的125 (OH)2D的作用。目前的综述详细介绍了这些新的发展,特别是与维生素D先天免疫调节相关的代谢和信号机制以及对人类疾病的影响。
An immunomodulatory role for vitamin D was first proposed more than 25 years ago, based on two salient observations. Firstly it was shown that monocytes/macrophages from patients with the granulomatous disease sarcoidosis constitutively synthesize the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) from precursor 25-hydroxyvitamin D (25OHD). Secondly, the receptor for 1,25(OH)2D (vitamin D receptor, VDR) is detectable in activated, proliferating lymphocytes. These observations suggested a mechanism whereby 1,25(OH)2D produced by monocytes could act upon adjacent T-cells or B-cells, but the impact of such a system on normal immune regulation was uncertain. Indeed, it is only in recent years that a much clearer picture of the role of vitamin D as a determinant of immune responsiveness has emerged. Two new concepts have prompted this change. Firstly studies of innate immunity have shown that intracrine induction of antimicrobial activity by vitamin D is a pivotal component of monocye/macrophage response to infection. Secondly, it is now clear that sub-optimal vitamin D status is a common feature of many populations throughout the world, with the potential to compromise monocyte/macrophage metabolism of 25OHD and subsequent actions of 1,25(OH)2D. The current review details these new developments with specific reference to the metabolic and signaling mechanisms associated with innate immune regulation by vitamin D and implications for human disease.
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