Abstract
Tumor necrosis factor α (TNFα) is a key pathogenic factor in Crohn's disease and rheumatoid arthritis. TNF(ΔARE) mice express high levels of TNFα and present Crohn's-like ileitis and arthritis. Alterations in the chemokine network could underline the TNF-driven ileitis. The aim of this study was to evaluate the role of TNF and chemokines in ileitis using ectromelia virus cytokine response modifier D (CrmD), a protein that binds TNFα and a limited number of chemokines. We generated transgenic mice expressing CrmD in intestinal epithelial cells (vCrmD mice) and crossed them with the TNF(ΔARE) mice to test whether CrmD could affect TNF-driven inflammatory processes. During homeostasis, only the number of B cells in the lamina propria was reduced by CrmD expression. Interestingly, CrmD expression in the intestine markedly attenuated the inflammatory infiltrates in the ileum of TNF(ΔARE) mice, but did not affect development of arthritis. Our results suggest that CrmD affects development of ileitis by locally affecting both TNF and chemokine function in the ileum.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arthritis
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism*
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B-Lymphocytes / pathology
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Carrier Proteins / metabolism
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Cells, Cultured
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Crohn Disease / genetics
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Crohn Disease / immunology*
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Crohn Disease / pathology
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Crohn Disease / physiopathology
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Disease Models, Animal
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Ectromelia virus / immunology*
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Humans
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Ileitis
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Inflammation
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism*
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Intestinal Mucosa / pathology
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Mice
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Mice, Mutant Strains
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Mice, Transgenic
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Mutation / genetics
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / immunology
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Receptors, Tumor Necrosis Factor / metabolism*
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Rheumatic Fever / genetics
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Rheumatic Fever / immunology*
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Rheumatic Fever / pathology
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Rheumatic Fever / physiopathology
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Transgenes / genetics
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism*
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Viral Proteins / genetics
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Viral Proteins / immunology
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Viral Proteins / metabolism*
Substances
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Carrier Proteins
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Receptors, Tumor Necrosis Factor
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Tumor Necrosis Factor-alpha
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Viral Proteins