Natural killer T cells mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice (IRM7P.478)

Abstract

Abstract Active vitamin D (1,25(OH)2D3) completely blocks the development of experimental autoimmune diseases. However, the molecular and immunobiological mechanisms underlying vitamin D’s anti-inflammatory properties are not fully understood. In the present study, we have employed a murine model of experimental autoimmune encephalomyelitis (EAE) in order to determine the role of natural killer T (NKT) cells in vitamin D-mediated protection from EAE. WT mice or mice deficient in all NKT cells (CD1d-/-) or invariant NKT (iNKT) cells (Jα18-/-) were fed control or 1,25(OH)2D3 (50 ng/day) supplemented diets. All mice fed control diet developed severe EAE. 1,25(OH)2D3treatment protected WT mice, but not CD1d-/- or Jα18-/- mice, from developing EAE. Development and severity of EAE were associated with insufficient suppression of the MOG-specific IL-17 response by 1,25(OH)2D3 treatment in CD1d-/- mice compared to WT mice. Activation of iNKT cells with α-galactosylceramide (α-GalCer) or 1,25(OH)2D3 treatment did not protect IL-4-/- mice from developing EAE. Furthermore, 1,25(OH)2D3 treatment of splenocytes in vitro resulted in decreased α-GalCer-induced IL-17 and increased IL-4 production. These studies demonstrate that NKT cells are important mediators of vitamin D-induced protection from EAE in mice and NKT cell-derived IL-4 may be an important factor in providing this protection.