Natural killer T cells ameliorate antibody-induced arthritis in macrophage migration inhibitory factor transgenic mice.

Takagi D, Iwabuchi K, Maeda M, Nakamaru Y, Furuta Y, Fukuda S, Van Kaer L, Nishihira J, OnoƩ K
Int J Mol Med. 2006 18 (5): 829-36

PMID: 17016612

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.

MeSH Terms (17)

Animals Antibodies, Monoclonal Antigens, CD Antigens, Differentiation, T-Lymphocyte Arthritis, Experimental Collagen Type II Galactosylceramides Interleukin-4 Interleukin-6 Killer Cells, Natural Lectins, C-Type Lipopolysaccharides Macrophage Migration-Inhibitory Factors Mice Mice, Inbred C57BL Mice, Transgenic T-Lymphocytes

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