Abstract
Macrophage migration inhibitory factor (MIF) is a cytokine that plays a critical role in the regulation of macrophage effector functions and T cell activation. However, its role in the pathogenesis of T cell-mediated autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE), has remained unresolved. In this study, we report that anti-MIF Ab treatment of SJL mice with acute EAE improved the disease severity and accelerated the recovery. Furthermore, the anti-MIF treatment impaired the homing of neuroantigen-reactive pathogenic T cells to the CNS in a VCAM-1-dependent fashion. Interestingly, MIF blockade also decreased the clonal size of the neuroantigen-specific Th1 cells and increased their activation threshold. Taken together, the results demonstrate an important role for MIF in the pathogenesis of EAE/multiple sclerosis and suggest that MIF blockade may be a promising new strategy for the treatment of multiple sclerosis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute Disease
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Animals
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Cell Movement / immunology*
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Cells, Cultured
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Central Nervous System / immunology*
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Central Nervous System / metabolism
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Central Nervous System / pathology
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Dose-Response Relationship, Immunologic
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Down-Regulation / immunology
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Encephalomyelitis, Autoimmune, Experimental / prevention & control*
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Epitopes, T-Lymphocyte / immunology
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Female
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Immune Sera / administration & dosage
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Injections, Intraperitoneal
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Lymphocyte Activation / immunology
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Lymphocyte Count
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Macrophage Migration-Inhibitory Factors / antagonists & inhibitors*
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Macrophage Migration-Inhibitory Factors / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Myelin Proteolipid Protein / immunology
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Peptide Fragments / immunology
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Severity of Illness Index
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / pathology
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Vascular Cell Adhesion Molecule-1 / biosynthesis
Substances
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Epitopes, T-Lymphocyte
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Immune Sera
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Macrophage Migration-Inhibitory Factors
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Myelin Proteolipid Protein
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Peptide Fragments
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Vascular Cell Adhesion Molecule-1
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myelin proteolipid protein (139-151)