NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice

Amanda Waddell, Jun Zhao, Margherita T. Cantorna

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29 Scopus citations


Active vitamin D [1,25-dihydroxyvitamin D3 (1,25D3)] blocks the development of experimental autoimmune diseases. However, the molecular and immunobiological mechanisms underlying 1,25D3's anti-inflammatory properties are not fully understood. We employed a murine model of experimental autoimmune encephalomyelitis (EAE) in order to determine the role of NKT cells in 1,25D3-mediated protection from EAE. Wild-type (WT) mice or mice lacking all NKT cells (CD1d-/-) or invariant NKT cells (Jα18-/-) were fed control or 1,25D3-supplemented diets. All mice fed with the control diet developed severe EAE. 1,25D3 treatment of WT mice protected them from developing EAE. CD1d-/- and Jα18-/- mice treated with 1,25D3 were not protected to the same extent as WT mice. Myelin oligodendrocyte glycoprotein-specific IL-17 and IFN-γ production was significantly reduced in 1,25D3 WT mice compared with WT but was not decreased in 1,25D3 CD1d-/- mice compared with CD1d-/- mice. IL-4-/- mice were utilized to determine how IL-4 deficiency affects susceptibility to EAE. IL-4-/- mice were not protected from developing EAE by α-galactosylceramide (α-GalCer) or 1,25D3 treatment. Furthermore, 1,25D3 treatment of splenocytes in vitro decreased α-GalCer-induced IL-17 and increased IL-4, IL-5 and IL-10 production. 1,25D3 alters the cytokine profile of invariant NKT cells in vitro. These studies demonstrate that NKT cells are important mediators of 1,25D3-induced protection from EAE in mice and NKT cell-derived IL-4 may be an important factor in providing this protection.

Original languageEnglish (US)
Pages (from-to)237-244
Number of pages8
JournalInternational immunology
Issue number5
StatePublished - May 1 2015

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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