Vitamin D and immune function: autocrine, paracrine or endocrine?

Prominent amongst the non-classical effects of vitamin D is its interaction with the immune system. Although this has been recognized for many years, it is only through recent studies that we have been able to fully understand the impact of vitamin D on normal innate and adaptive immune function. In particular these studies have illustrated how impaired vitamin D status has important ramifications for dysregulated immune responses to infection and aberrant inflammatory responses associated with autoimmune disease. Indeed it seems likely that the effects of vitamin D will extend beyond these established immune diseases to include additional novel effects, such as interaction with the enteric gut microbiota. Central to this new perspective on vitamin D and immunity has been the elucidation of pivotal mechanisms that underpin the interface between vitamin D and target immune cells. In particular, it is now clear that effects of vitamin D on monocytes, macrophages, dendritic cells, and lymphocytes are not constrained by the metabolic pathways associated with classical endocrine actions of vitamin D. Instead, it is now important to also consider intracrine and paracrine pathways that are subject to a distinct set of modulatory signals, and which may also be influenced by disease-specific dysregulation. The current review will discuss this by comparing the intracrine, paracrine and endocrine metabolic systems that influence the interaction between vitamin D and the immune system.