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Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity
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Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity
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Journal Article
Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity
2008
Overview
Beyond the classical effects of vitamin D on bone and calcium homeostasis, nonclassical effects in cancer and cardiovascular disease are emerging. This article details another important nonclassical role for vitamin D in regulating both innate and adaptive immunity, and how this can become compromised by vitamin D insufficiency.
Knowledge about the ability of vitamin D to function outside its established role in skeletal homeostasis is not a new phenomenon. Nonclassical immunomodulatory and antiproliferative responses triggered by active 1,25-dihydroxyvitamin D were first reported more than a quarter of a century ago. It is only in recent years, however, that there has been a significant improvement in our understanding of how these nonclassical effects of vitamin D can influence the pathophysiology and possible prevention of human disease. Three particular strands of evidence have been prominent: firstly, population studies have revised our interpretation of normal vitamin D status in humans, suggesting, in turn, that vitamin D insufficiency is a clinical problem of global proportions; secondly, epidemiology has linked vitamin D status with disease susceptibility and/or mortality; and, thirdly, expression of the machinery required to synthesize 1,25-dihydroxyvitamin D in normal human tissue seems to be much more widespread than originally thought. Collectively, these observations suggest that nonclassical metabolism and response to vitamin D might have a significant role in human physiology beyond skeletal and calcium homeostasis. Specific examples of this will be detailed in the current Review, with particular emphasis on the immunomodulatory properties of vitamin D.
Key Points
Nonclassical effects of vitamin D have been recognized for many years, but it is only recently that these have been accepted as a potentially significant component of vitamin D physiology
Immune cells such as macrophages contain all of the machinery required to synthesize and respond to active vitamin D, 1,25-dihydroxyvitamin D, and these functions are enhanced by challenge to the immune system
1,25-Dihydroxyvitamin D stimulates innate (macrophage) immunity by enhancing bacterial killing but it also modulates adaptive (lymphocyte) immunity to minimize inflammation and autoimmune disease
Vitamin D insufficiency is now a global health issue—even in developed countries
Vitamin D insufficiency is associated with compromised immunity, leading to increased infectious diseases such as tuberculosis, and increased susceptibility to autoimmune diseases such as type 1 diabetes
Publisher
Nature Publishing Group UK,Nature Publishing Group
