Abstract
Vitamin D was originally discovered for its critical role in calcium homeostasis. However, it is now known that vitamin D has pleiotropic actions, and one of the more active areas of recent vitamin D research has focused on understanding its role as a modulator of immune system function. The past few years have provided a wealth of data to support a fundamental role for vitamin D signaling in regulating innate immunity in humans and a firm molecular basis for the numerous studies linking vitamin D deficiency with increased rates of infectious diseases. It is also now known that stimulation of naïve macrophages through toll-like receptors (TLRs) strongly enhances vitamin D signaling through induction of CYP27B1 and vitamin D receptor (VDR) expression, which leads to production of hormonal 1,25(OH)2D3, and that the magnitude of this production is strongly dependent on ambient 25(OH)D3 concentrations. 1,25(OH)2D3 thus produced signals via the VDR to induce expression of key components of innate immune responses such as AMPs and the pattern recognition receptor NOD2. There is likely more to uncover in this area. In addition, the recognition of the importance of vitamin D in controlling innate immune function should spur renewed interest in developing vitamin D analogs that may find roles, if not as front-line therapies for infectious disease, as components of combined therapies to treat emerging antibiotic-resistant disease.
Published Version
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