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The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor.
Journal of Experimental Medicine
Date de publication
The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2), which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor. CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome 21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By approximately 12 wk of age, the majority of mutant mice raised in a conventional facility developed a chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10-deficient mice. These findings suggest that CRF2-4 is essential for IL-10-mediated effects and is a subunit of the IL-10 receptor.
Animals, Cell Separation, Cells, Cultured, Colitis/immunology, Flow Cytometry, Interferon-alpha/pharmacology, Interferon-gamma/pharmacology, Interleukin-10 Receptor beta Subunit, Lymphocytes/drug effects, Lymphocytes/immunology, Macrophages/drug effects, Macrophages/immunology, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Protein Conformation, Receptors, Cytokine/genetics, Receptors, Cytokine/immunology, Receptors, Interleukin/genetics, Receptors, Interleukin/immunology, Receptors, Interleukin-10, Splenomegaly/immunology, Stem Cells/drug effects, Stem Cells/immunology, Transfection
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