title: Natural killer T cells ameliorate antibody-induced arthritis in macrophage migration inhibitory factor transgenic mice.
abstract: Macrophage migration inhibitory factor (MIF) plays an important role in inflammatory diseases. It has been reported that anti-MIF treatment and mif-gene disruption ameliorate joint inflammation in a mouse model of arthritis induced by anti-type II collagen monoclonal antibodies and lipopolysaccharide (anti-IIC mAb/LPS). In the present study, using the anti-IIC mAb/LPS system, we have analyzed arthritis in MIF-transgenic (MIFTg) and wild-type C57BL/6 (WT) mice. We found that MIFTg mice developed more severe arthritis than WT mice. The histopathological scores were significantly higher in MIFTg mice and significantly increased numbers of CD69+ T cells were detected in the spleens of these arthritic MIFTg mice, compared with WT mice. Natural killer T (NKT) cells from MIFTg mice, compared with WT mice, produced reduced amounts of IL-4 upon stimulation with agr;-galactosylceramide (alpha-GalCer). Further, repeated administration of alpha-GalCer to MIFTg mice resulted in a profound reduction of both clinical and histopathological scores of arthritis, with a significant decrease in IL-6. The present findings demonstrate that overexpression of MIF exacerbates inflammation in this arthritis model and that NKT cells play an ameliorating role upon stimulation with alpha-GalCer in the inflammatory process in MIFTg mice.
authors.affiliation: Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Takagi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Maeda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamaru
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Furuta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuda
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.forename: Kazunori
authors.initials: K
authors.lastname: Onoé
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology; D005699:Galactosylceramides / Q000008:administration & dosage; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D024043:Collagen Type II; D005699:Galactosylceramides; D015847:Interleukin-4; D015850:Interleukin-6; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D000099192:CD69 Antigens; C493154:alpha-galactosylceramide