Abstract
The chemokine monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 have been shown to play an important role in the migration and trafficking of macrophages and Th1 effector cells in experimental autoimmune encephalomyelitis. Also, MCP-1 has been reported to regulate oral tolerance induction by inhibition of Th1 cell-related cytokines and by the ability of Abs to MCP-1 to inhibit oral tolerance. This study demonstrates that neither MCP-1 nor its receptor CCR2 is required for the induction of oral tolerance. Mice deletional for either MCP-1 or CCR2 had suppressed cell-proliferative and Th1 responses following oral administration and immunization with myelin oligodendrocyte glycoprotein (MOG(35-55)). TGF-beta was up-regulated in fed and immunized deletional mice, while IL-4 was absent from deletional mice, but up-regulated in controls. Decreased experimental autoimmune encephalomyelitis severity was found in MOG(35-55)-fed MCP-1 deletional mice, indicating induction of oral tolerance. These results demonstrate that MCP-1 is not required for induction of oral tolerance and that MCP-1 and CCR2 are essential for up-regulation of IL-4 in tolerized mice.
Publication types
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Comparative Study
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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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Administration, Oral
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Animals
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Cells, Cultured
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Chemokine CCL2 / deficiency*
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Chemokine CCL2 / genetics*
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Chemokine CCL2 / metabolism
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Dose-Response Relationship, Immunologic
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Female
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Glycoproteins / administration & dosage
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Glycoproteins / immunology
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Immune Tolerance / genetics*
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Immunohistochemistry
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Injections, Subcutaneous
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Interleukin-4 / biosynthesis
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Intestinal Mucosa / chemistry
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism
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Intubation, Gastrointestinal
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Lymphoid Tissue / chemistry
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Lymphoid Tissue / immunology
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Lymphoid Tissue / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / administration & dosage
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Peptide Fragments / immunology
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Receptors, CCR2
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Receptors, Chemokine / deficiency*
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Receptors, Chemokine / genetics*
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Ccr2 protein, mouse
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Chemokine CCL2
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Glycoproteins
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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Receptors, CCR2
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Receptors, Chemokine
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myelin oligodendrocyte glycoprotein (35-55)
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Interleukin-4