Vitamin D and immune function

Abstract

Vitamin D metabolizing enzymes and vitamin D receptors are present in many cell types including various immune cells such as antigen-presenting-cells, T cells, B cells and monocytes. In vitro data show that, in addition to modulating innate immune cells, vitamin D also promotes a more tolerogenic immunological status. In vivo data from animals and from human vitamin D supplementation studies have shown beneficial effects of vitamin D on immune function, in particular in the context of autoimmunity. In this review, currently available data are summarized to give an overview of the effects of vitamin D on the immune system in general and on the regulation of inflammatory responses, as well as regulatory mechanisms connected to autoimmune diseases particularly in type 1 diabetes mellitus.

Figure 1

Mechanisms for innate and adaptive immune responses to vitamin D. Cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) are metabolized in the liver to form 25-hydroxyvitamin D (25D), the main circulating form of vitamin D. Target cells such as monocytes/macrophages and dendritic cells (DC) expressing the vitamin D-activating enzyme CYP27B1 and the vitamin D receptor (VDR) can then utilize 25D for intracrine responses via localized conversion to calcitriol (1,25D). In monocytes/macrophages this promotes antibacterial response to infection. In DCs, intracrine synthesis of 1,25D inhibits DC maturation, thereby modulating helper T-cell (Th) function. Th responses to 25D may also be mediated in a paracrine fashion, with DC-generated 1,25D. Intracrine immune effects of 25D also occur in CYP27B1/VDR-expressing epithelial cells. However, other cells such as neutrophils do not appear to express CYP27B1 and are therefore likely to be affected by circulating levels of 1,25D synthesized by the kidneys. VDR-expressing Th are also potential targets for systemic 1,25D, although intracrine mechanisms have also been proposed. In a similar fashion, epithelial cells, trophoblasts and decidual cells are all able to respond in an intracrine fashion to 25D, but may also respond to systemic 1,25D to promote antibacterial responses. With permission from Clinical Endocrinology [2].