Potential of targeting natural killer T cells for the treatment of autoimmune diseases |
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Authors: | Email author" target="_blank">Sachiko?MiyakeEmail author Asako?Chiba Takashi?Yamamura |
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Institution: | (1) Department of Immunology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan |
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Abstract: | Natural killer (NK) T cells emerge as unique lymphocytes subsets implicated in the regulation of autoimmunity. Abnormalities
in the numbers and functions of NKT cells have been observed in patients with diverse autoimmune diseases as well as in a
variety of mouse strains that are genetically predisposed for the development of autoimmune diseases. Unlike conventional
T cells that recognize peptides in association with major histocompatibility complex (MHC), NKT cells recognize glycolipid
antigens presented by the nonpolymorphic MHC class I-like protein, CD1d. Recently, vigorous activation of NKT cells by synthetic
glycolipids such as α-galactosylceramide (α-GC) or its sphingosine truncated derivative OCH have been shown to suppress autoimmune
diseases such as experimental auto-immune encephalomyelitis (EAE), diabetes in nonobese diabetic (NOD) mice, and collagen-induced
arthritis (CIA) by inducing T helper (Th) 2 bias of autoimmune T cells. In this review, we examine the potential roles of
NKT cells in the pathogenesis of autoimmune disease regulation, and the recent advances in glycolipid therapy for autoimmune
disease models. In addition, we summarize studies suggesting a role for NKT cells in human autoimmune disease, and discuss
the potential of targeting NKT cells for the treatment of autoimmunity. |
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Keywords: | α -Galactosylceramide (α -GC) Autoimmune disease Natural killer (NK) T cells OCH Th1/Th2 |
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