Vitamin D3and the immune system: maintaining the balance in health and disease

Abstract

1,25-Dihydroxyvitamin D3(1,25(OH)2D3), the active form of vitamin D3, is a central player in Ca and bone metabolism. More recently, important immunomodulatory effects have been attributed to this hormone. By binding to its receptor, the vitamin D receptor, 1,25(OH)2D3regulates the expression of various genes and consequently affects the behaviour of different cell types within the immune system. 1,25(OH)2D3can potently inhibit pathogenic T cells and gives rise to elevated numbers of regulatory T cells via the induction of tolerogenic dendritic cells. These immunomodulatory activities of 1,25(OH)2D3have also been proven usefulin vivo: administration of 1,25(OH)2D3in several animal models can prevent or cure different autoimmune diseases and graft rejection. To overcome the dose-limiting side effects of 1,25(OH)2D3on Ca and bone, less calcaemic structural analogues (alone or in combination with synergistically acting drugs or bone-resorption inhibitors) have been successfully used in animal models. Furthermore, as 1,25(OH)2D3also contributes to host defence against infectious agents by the induction of antimicrobial responses, this molecule might provide a new strategy to deal with drug-resistant infections. According to the pleiotropic effects of 1,25(OH)2D3in the immune system, increasing epidemiological data underline the importance of adequate vitamin D intakes in reducing the risk of several autoimmune diseases and infections such as tuberculosis.