The Orphan Receptor CRF2-4 Is an Essential Subunit of the Interleukin 10 Receptor
Copyright policy )The Orphan Receptor CRF2-4 Is an Essential Subunit of the Interleukin 10 Receptor
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 ∼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.
- UNIVERSITY OF CALIFORNIA SAN FRANCISCO
- San Francisco VA Medical Center United States
- GENENTECH INC United States
- San Francisco VA Health Care System United States
Membrane Glycoproteins, Protein Conformation, Macrophages, Stem Cells, Interferon-alpha, Cell Separation, Receptors, Interleukin, Colitis, Flow Cytometry, Interleukin-10 Receptor beta Subunit, Transfection, 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, Mice, Inbred C57BL, Interferon-gamma, Mice, Splenomegaly, Animals, Receptors, Interleukin-10, Lymphocytes, Receptors, Cytokine, Cells, Cultured
Membrane Glycoproteins, Protein Conformation, Macrophages, Stem Cells, Interferon-alpha, Cell Separation, Receptors, Interleukin, Colitis, Flow Cytometry, Interleukin-10 Receptor beta Subunit, Transfection, 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, Mice, Inbred C57BL, Interferon-gamma, Mice, Splenomegaly, Animals, Receptors, Interleukin-10, Lymphocytes, Receptors, Cytokine, Cells, Cultured
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