Arch Biochem Biophys 2002 Dec 15;408(2):200-4
Meehan TF, DeLuca HF.
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, 53706, Madison, WI, USA
The active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D(3), suppresses autoimmune disease in several animal models including experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis.
The molecular mechanism of this immunosuppression is at present unknown.
While 1alpha,25-dihydroxyvitamin D(3) is believed to function through a single vitamin D receptor, there are reports of other vitamin D receptors as well as a "nongenomic" mode of action.
We have prepared the EAE model possessing the vitamin D receptor null mutation and determined if 1alpha,25-dihydroxyvitamin D(3) can suppress this disease in the absence of a functional vitamin D receptor.
Vitamin D receptor null mice develop EAE although the incidence rate is one-half that of wild-type controls.
The administration of 1alpha,25-dihydroxyvitamin D(3) had no significant effect on the incidence of EAE in the vitamin D receptor null mice, while it completely blocked EAE in the wild-type mice.
We conclude that 1alpha,25-dihydroxyvitamin D(3) functions to suppress EAE through the well-known VDR and not through an undiscovered receptor or through a "nongenomic" mechanism.