Vitamin D metabolism and innate immunity

Abstract

Effects of vitamin D on the immune system have been recognized for over 30 years and stemmed in part from analysis of the dysregulated vitamin D metabolism associated with granulomatous diseases. However, it is only in more recent years that a role for interaction between vitamin D and normal immune function has been proposed. As with the original studies, the basis for this new perspective on immunomodulation by vitamin D stems from studies of vitamin D metabolism by immune cells. In particular, induction of the vitamin D-activating enzyme CYP27B1 in monocytes via pathogen recognizing receptors has highlighted an entirely new function for vitamin D as a potent inducer of antibacterial innate immune responses. This has prompted a new potential role for vitamin D in protecting against infection in a wide range of tissues but has also prompted revision of the parameters for adequate vitamin D status. The following review describes some of the key developments in innate immune responses to vitamin D with particular emphasis on the role of key metabolic enzyme as determinants of localized immune activity of vitamin D.

Figure 1. Vitamin D metabolism and innate immune responses

Metabolism of 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25(OH)₂D) by monocytes and the intracrine regulation of antibacterial activity (DEFB4/LL37 production and autophagy), antigen presentation (decreased HLA-DR, CD83 and CD86) and T-cell (Th1, Th2, Th17 and Treg) function (solid arrows). Effects of toll-like receptor (TLR)-mediated response to pathogens such as Mycobacterium tuberculosis (M. tb), and associated cytokine effects on monocyte vitamin D metabolism are show by dashed lines. Effects of cytokines and NOD2 intracellular pathogen recognition on nuclear factor-κB (NF-κB) enhancement of vitamin D-receptor (VDR)-retinoid X receptor (RXR)-mediated transcription of antibacterial factors are shown as solid gray lines.