Functional effects of vitamin D: From nutrient to immunomodulator

Vitamin D can be obtained from the endogenous synthesis in the epidermis by exposure to UVB light, and from foods and supplements in the form of ergocalciferol (vitamin D₂) and cholecalciferol (vitamin D₃). The main metabolite used to measure vitamin D serum status is calcidiol [25(OH)D]. However, its active metabolite calcitriol [1α,25(OH)₂D] performs pleiotropic effects in the cardiovascular, neurological, and adipose tissue as well as immune cells. Calcitriol exerts its effects through genomic mechanisms modulated by the nuclear vitamin D receptor (VDR)/retinoid X receptor (RXR) complex, to bind to vitamin D response elements (VDRE) in target genes of several cells such as activated T and B lymphocytes, neutrophils, macrophages, and dendritic cells; besides of its genomic mechanisms, VDR performs novel non-genomic mechanisms that involve its membrane expression and soluble form; highlighting that vitamin D could be an immunomodulatory nutrient that plays a key role during physiological and pathological events. Therefore, the aim of this comprehensive literature review was to describe the most relevant findings of vitamin D dietary sources, absorption, synthesis, metabolism, and factors that influence its serum status, signaling pathways, and biological effects of this immunonutrient in the health and disease.