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Vitamin D Receptor and immune differences between mice and men – Sept 2015

Species-specific regulation of innate immunity by vitamin D signaling

The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2015.09.016
Vassil Dimitrov, John H. White,
•The hormonal form of vitamin D, 1,25-dihydroxyvitamin D, is a key regulator of innate immunity.
•In humans, the activated vitamin D receptor (VDR) is a direct regulator of transcription of genes encoding antimicrobial peptides, pattern recognition receptors, and innate immune cytokines.
•While regulation of VDR target genes implicated in innate immunity in humans appears to be widely conserved in primates, the regulation is not conserved in mice.
•Given the increasing evidence that vitamin D signaling can regulate innate immunity in mice, the combined data indicate that the mechanisms of innate immune regulation by vitamin D are species-specific.


Rodent studies of vitamin D may sometimes not carry over to human studies

While many global mechanisms of innate immune responses to pathogen threat are conserved over a vast range of species, the details of those responses and their regulation appear to be highly species-specific. An array of studies over recent years has revealed that hormonal vitamin D is an important regulator of innate immunity. In humans, the hormone-bound VDR directly induces the transcription of genes encoding antimicrobial peptides (AMPs), pattern recognition receptors and key cytokines implicated in innate immune responses.
We find that the vitamin D response elements (VDREs) in a number of these human genes are highly conserved in a range of primates, but not present in rodent genes.

Consistent with this, VDR target genes encoding AMPs human beta-defensin 2 (HBD2) and cathelicidin (CAMP) and the pattern recognition receptor NOD2 are induced by 1,25(OH)2D in human cells of epithelial or myeloid origin but not similarly regulated in mouse cells. In addition, while conditioned media from human epithelial cells treated with 1,25(OH)2D produced antimicrobial activity against E. coli and the lung pathogen P. aeruginosa, no such activity was detected in conditioned media from comparable 1,25(OH)2D-treated mouse epithelial cells. Given that other work has provided evidence that 1,25(OH)2D does control innate immune responses in mouse models of disease, we discuss the species-specific similarities and differences in 1,25(OH)2D-regulated innate immunity.

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