Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
John H White
McGill University, Canada
Posters & Accepted Abstracts: J Clin Cell Immunol
Hormonal 1,25-dihydroxyvitamin D (1,25D) signals through the nuclear vitamin-D receptor (VDR), a ligand-regulated transcription factor. Vitamin-D was discovered as the cure to nutritional rickets and 1,25D is a critical regulator of calcium homeostasis during development and in the adult. However, the VDR is expressed in several tissues not implicated in calcium homeostasis, including throughout the immune system and a wide range of studies over recent years has revealed that hormonal vitamin-D is an important regulator of innate immunity. In humans, the 1,25D-bound VDR directly induces the transcription of genes encoding antimicrobial peptides (AMPs), pattern recognition receptors and key cytokines implicated in innate immune responses. These findings provide a molecular basis for a number of clinical studies providing a correlation between vitamin-D deficiency and an increased risk of infection. Notably, while global mechanisms of innate immune responses to pathogen threat have been conserved during evolution, the details of those responses and their regulation are species-specific. We find that the cognate binding sites for the VDR (vitamin D response elements; VDREs) present in a number of human genes encoding key components of innate immune responses are highly conserved in primates, but not present in rodent genes. Similarly, 1,25D-induced production of AMPs appears to be absent in mice. Given that other work has shown that 1,25D does control innate immune responses in rodent models of disease, the similarities and differences in 1,25D-regulated innate immune responses between species will be discussed.