title: NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice.
abstract: 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.
authors.affiliation: Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Waddell
authors.affiliation: Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA mxc69@psu.edu.
authors.forename: Margherita T
authors.initials: MT
authors.lastname: Cantorna
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics; D001324:Autoantigens / Q000276:immunology; D002117:Calcitriol / Q000276:immunology* / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000502:physiology*
chemical_list: D055610:Antigens, CD1d; D001324:Autoantigens; D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D015847:Interleukin-4; D002117:Calcitriol
keywords: EAE; NKT cells; vitamin D