Development of experimental autoimmune encephalomyelitis (EAE) in mice requires vitamin D and the vitamin D receptor

Proc Natl Acad Sci U S A. 2012 May 29;109(22):8501-4. doi: 10.1073/pnas.1206054109. Epub 2012 May 16.

Abstract

The development of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, has been studied in mice that were (i) vitamin D-deficient, (ii) minus the vitamin D receptor, (iii) minus a vitamin D 25-hydroxylase, and (iv) minus the vitamin D 25-hydroxyvitamin D-1α-hydroxylase. EAE development was markedly suppressed in mice lacking the vitamin D receptor and partially suppressed in vitamin D-insufficient mice. However, the absence of either of the two key hydroxylases (i.e., 25-hydroxylase and 1α-hydroxylase) neither inhibits nor enhances the development of EAE. These results indicate that vitamin D and the vitamin D receptor are required for the development of EAE. The results also suggest that 1,25-dihydroxyvitamin D(3) may not play a role in this autoimmune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism*
  • Animals
  • Body Weight
  • Calcium / administration & dosage
  • Calcium / blood
  • Calcium / metabolism
  • Cholestanetriol 26-Monooxygenase / genetics
  • Cholestanetriol 26-Monooxygenase / metabolism*
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Female
  • Glycoproteins / immunology
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments / immunology
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism*
  • Vitamin D / administration & dosage
  • Vitamin D / blood
  • Vitamin D / metabolism*
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / metabolism

Substances

  • Glycoproteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Receptors, Calcitriol
  • myelin oligodendrocyte glycoprotein (35-55)
  • Vitamin D
  • Cyp2r1 protein, mouse
  • Cholestanetriol 26-Monooxygenase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcium