Effects of vitamin D on antigen-specific and non-antigen-specific immune modulation: relevance for type 1 diabetes

Vitamin D is a fat-soluble precursor of the circulating 25-hydroxyvitamin D₃ (25(OH)D₃)which can be converted by the 1α-hydroxylase (1α(OH)ase) enzyme into the bioactive hormonal metabolite 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), generally known to promote bone mineralization through its ability to enhance calcium absorption from the gut. Importantly, in humans, vitamin D is mainly derived from endogenous production of vitamin D₃ from ultraviolet (UV) radiation exposure to the skin while a small part (<10%) is obtained via dietary intake of dairy products and fatty fish (1). Taking these factors into account, geographic distribution and seasonality, skin pigmentation, age, and lifestyle may predispose certain populations to be at a higher risk of developing vitamin D insufficiency or deficiency (2). The first valid reports correlating the importance of an adequate vitamin D status to optimal human health originate from the early part of the 20th century, when vitamin D was described to prevent and treat the bone disease rickets. Since then, the findings that vitamin D receptors (VDR) are present in many body tissues and that vitamin D metabolizing enzymes can be found in various cells outside the kidney, including the intestine, prostate, immune cells, and within the skin itself (reviewed in reference 3), have revolutionized the vitamin D business. In this review, we will mainly focus on vitamin D as a component of immune regulation and on the role of vitamin D in antigen-specific and non-specific therapies with potential relevance for type 1 diabetes (T1D).