Department of Physiology, McIntyre Bldg., Rm. 1112, 3655 Drummond St., Montreal, Qc, Canada H3G 1Y6.
Arch Biochem Biophys. 2012 Jul 1;523(1):58-63. doi: 10.1016/j.abb.2011.11.006. Epub 2011 Nov 15.
Vitamin D was discovered as the cure for nutritional rickets. Classically, hormonal 1,25-dihydroxyvitamin D (1,25D), produced in the kidney by CYP27B1-catalyzed 1α-hydroxylation from its circulating 25-hydroxy precursor, has been considered to function as a critical endocrine regulator of calcium homeostasis. However, our appreciation of vitamin D metabolism and physiological function has evolved dramatically in recent years. First, vitamin D is now recognized as a pleiotropic regulator of human physiology, with emerging roles in cancer chemoprevention, cardio-protection, and, in particular, regulation of immune system functions. Moreover, CYP27B1 is very widely expressed, and evidence is rapidly accumulating that local CYP27B1-catalyzed production of 1,25D, controlled by tissue-specific signals, is critical for its physiological actions. Nowhere is this more apparent than in the innate immune system, where recent studies have shown that CYP27B1 expression is under control of several immune signaling pathways, and that signaling by 1,25D in macrophages and dendritic cells is critical for innate immune responses to infection. This review will describe our current knowledge of the signaling pathways that lead to 1,25D production in the immune system and the downstream signaling events it controls in response to pathogen recognition.
维生素 D 被发现是营养性佝偻病的治疗方法。经典地，由 CYP27B1 催化的 1α-羟化作用从其循环的 25-羟前体产生的激素 1,25-二羟维生素 D（1,25D），被认为是钙稳态的关键内分泌调节剂。然而，近年来我们对维生素 D 代谢和生理功能的认识发生了巨大的变化。首先，维生素 D 现在被认为是人类生理学的多效调节剂，在癌症化学预防、心脏保护以及特别是免疫系统功能的调节方面具有新兴作用。此外，CYP27B1 表达非常广泛，并且有证据表明，局部 CYP27B1 催化的 1,25D 产生受组织特异性信号的控制，对于其生理作用至关重要。这在先天免疫系统中最为明显，最近的研究表明，CYP27B1 表达受几种免疫信号通路的控制，并且 1,25D 在巨噬细胞和树突状细胞中的信号传导对于先天免疫反应至关重要。这篇综述将描述我们目前对导致免疫系统中 1,25D 产生的信号通路以及它在病原体识别时控制的下游信号事件的了解。
