IBMS BoneKEy | Perspective
Vitamin D and the immune system: Getting it right
Chantal Mathieu
DOI:10.1138/20110505
Abstract
1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, is an important player in calcium and bone metabolism, but 1,25(OH)2D3 also has a physiological role beyond its well-known role in skeletal homeostasis. Receptors for 1,25(OH)2D3 are present in various immune cells, including monocytes, macrophages and dendritic cells, as well as T and B lymphocytes, thus suggesting a role for 1,25(OH)2D3 in both innate and adaptive immune responses. Besides being targets, immune cells express vitamin D-activating enzymes, allowing local conversion of inactive vitamin D into 1,25(OH)2D3 within the immune system. Data from epidemiological studies are clear: vitamin D deficiency, especially in early life, increases the risk of autoimmune diseases later on and is associated overall with an increased risk of infections. Moreover, higher levels of 25(OH)D3 are associated with relative protection against infections and autoimmune diseases. These association data are corroborated by experiments in preclinical animal models, where data exist that even supplementing with high doses of vitamin D or analogues of 1,25(OH)2D3 can interfere with the course of immune diseases, especially autoimmune diseases like colitis, multiple sclerosis and type 1 diabetes. In humans, however, intervention trials demonstrating strong protection are lacking. This Perspective discusses the complex immune-regulatory effects of 1,25(OH)2D3 on immune cells as well as its role in infectious and autoimmune diseases, using tuberculosis and type 1 diabetes as examples.
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