Vitamin D and the immune system: new perspectives on an old theme.

Interaction with the immune system is one of the most well-established nonclassic effects of vitamin D. For many years this was considered to be a manifestation of granulomatous diseases such sarcoidosis, in which synthesis of active 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is known to be dysregulated. However, recent reports have supported a role for 1,25(OH)(2)D(3) in mediating normal function of the innate and adaptive immune systems. Crucially, these effects seem to be mediated via localized autocrine or paracrine synthesis of 1,25(OH)(2)D(3) from precursor 25-hydroxyvitamin D(3), the main circulating metabolite of vitamin D. The ability of vitamin D to influence normal human immunity is highly dependent on the vitamin D status of individuals, and may lead to aberrant response to infection or autoimmunity in those who are lacking vitamin D. The potential health significance of this has been underlined by increasing awareness of impaired vitamin D status in populations across the globe. This article describes some of the recent developments with respect to vitamin D and the immune system, and possible clinical implications.