Abstract
The IL-7/IL-7R-dependent signaling pathway plays a crucial role in regulating the immune response in intestinal mucosa. Here we demonstrate the pivotal role of this pathway in the development and treatment of chronic colitis. T cells expressing high levels of IL-7R were substantially infiltrated in the chronic inflamed mucosa of TCR alpha-chain knockout mice and IL-7 transgenic mice. Transfer of mucosal T cells expressing high levels of IL-7R, but not T cells expressing low levels of IL-7R, from these mice into recombinase-activating gene-2(-/-) mice induced chronic colitis. Selective elimination of T cells expressing high levels of IL-7R by administrating small amounts of toxin-conjugated anti-IL-7R Ab completely ameliorated established, ongoing colitis. These findings provide evidence that therapeutic approaches targeting mucosal T cells expressing high levels of IL-7R are effective in the treatment of chronic intestinal inflammation and may be feasible for use in the therapy of human inflammatory bowel disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / therapeutic use
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Cell Movement / genetics
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Cell Movement / immunology
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Chronic Disease
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Colitis / genetics
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Colitis / immunology*
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Colitis / pathology
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Colitis / therapy*
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Disease Models, Animal
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Genes, T-Cell Receptor alpha
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Immunoconjugates / administration & dosage
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Immunoconjugates / therapeutic use
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Immunotoxins / administration & dosage
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Immunotoxins / therapeutic use
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Injections, Intraperitoneal
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Intestinal Mucosa / cytology
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / metabolism*
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Intestinal Mucosa / transplantation
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Lymphocyte Transfusion
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, SCID
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N-Glycosyl Hydrolases / administration & dosage
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N-Glycosyl Hydrolases / therapeutic use
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Plant Proteins / administration & dosage
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Plant Proteins / therapeutic use
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Receptors, Interleukin-7 / biosynthesis*
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Receptors, Interleukin-7 / immunology
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Ribosome Inactivating Proteins, Type 1
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Saporins
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Severe Combined Immunodeficiency / genetics
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Severe Combined Immunodeficiency / immunology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / transplantation
Substances
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Antibodies, Monoclonal
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Immunoconjugates
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Immunotoxins
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Plant Proteins
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Receptors, Interleukin-7
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Ribosome Inactivating Proteins, Type 1
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N-Glycosyl Hydrolases
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Saporins