J. Exp. Med., Volume 187, Number 4, February 16, 1998 571-578

The Orphan Receptor CRF2-4 Is an Essential Subunit of the Interleukin 10 Receptor

By Susan D. Spencer,^* Francesco Di Marco, Jeff Hooley,^* Sharon Pitts-Meek,^* Michele Bauer,^* Anne M. Ryan,^* Bernard Sordat, Verna C. Gibbs,^§ and Michel Aguet

From the ^* Genentech Inc., South San Francisco, California 94080; the  Swiss Institute for Experimental Cancer Research, 1066 Epalinges s/Lausanne, Switzerland; and the ^§ Department of Surgery, San Francisco Veterans Affairs Medical Center, San Francisco, California 94121

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Rivera, A., Collins, N., Stephan, M. T., Lipuma, L., Leiner, I., Pamer, E. G. (2009). Aberrant Tissue Localization of Fungus-Specific CD4+ T Cells in IL-10-Deficient Mice. J. Immunol. 183: 631-641 [Abstract] [Full Text]  
• Xu, J., Yang, Y., Qiu, G., Lal, G., Wu, Z., Levy, D. E., Ochando, J. C., Bromberg, J. S., Ding, Y. (2009). c-Maf Regulates IL-10 Expression during Th17 Polarization. J. Immunol. 182: 6226-6236 [Abstract] [Full Text]  
• Biswas, P. S., Pedicord, V., Ploss, A., Menet, E., Leiner, I., Pamer, E. G. (2007). Pathogen-Specific CD8 T Cell Responses Are Directly Inhibited by IL-10. J. Immunol. 179: 4520-4528 [Abstract] [Full Text]  
• Weaver, B. K., Bohn, E., Judd, B. A., Gil, M. P., Schreiber, R. D. (2007). ABIN-3: a Molecular Basis for Species Divergence in Interleukin-10-Induced Anti-Inflammatory Actions. Mol. Cell. Biol. 27: 4603-4616 [Abstract] [Full Text]  
• Wise, L., McCaughan, C., Tan, C. K., Mercer, A. A., Fleming, S. B. (2007). Orf virus interleukin-10 inhibits cytokine synthesis in activated human THP-1 monocytes, but only partially impairs their proliferation. J. Gen. Virol. 88: 1677-1682 [Abstract] [Full Text]  
• Levraud, J.-P., Boudinot, P., Colin, I., Benmansour, A., Peyrieras, N., Herbomel, P., Lutfalla, G. (2007). Identification of the Zebrafish IFN Receptor: Implications for the Origin of the Vertebrate IFN System. J. Immunol. 178: 4385-4394 [Abstract] [Full Text]  
• Bharhani, M. S., Borojevic, R., Basak, S., Ho, E., Zhou, P., Croitoru, K. (2006). IL-10 protects mouse intestinal epithelial cells from Fas-induced apoptosis via modulating Fas expression and altering caspase-8 and FLIP expression.. Am. J. Physiol. Gastrointest. Liver Physiol. 291: G820-G829 [Abstract] [Full Text]  
• Spach, K. M., Nashold, F. E., Dittel, B. N., Hayes, C. E. (2006). IL-10 Signaling Is Essential for 1,25-Dihydroxyvitamin D3-Mediated Inhibition of Experimental Autoimmune Encephalomyelitis. J. Immunol. 177: 6030-6037 [Abstract] [Full Text]  
• Dang, P. M.-C., Elbim, C., Marie, J.-C., Chiandotto, M., Gougerot-Pocidalo, M.-A., El-Benna, J. (2006). Anti-inflammatory effect of interleukin-10 on human neutrophil respiratory burst involves inhibition of GM-CSF-induced p47PHOX phosphorylation through a decrease in ERK1/2 activity. FASEB J. 20: 1504-1506 [Abstract] [Full Text]  
• Frodsham, A. J., Zhang, L., Dumpis, U., Taib, N. A. M., Best, S., Durham, A., Hennig, B. J. W., Hellier, S., Knapp, S., Wright, M., Chiaramonte, M., Bell, J. I., Graves, M., Whittle, H. C., Thomas, H. C., Thursz, M. R., Hill, A. V. S. (2006). Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence. Proc. Natl. Acad. Sci. USA 103: 9148-9153 [Abstract] [Full Text]  
• Huang, B., Pan, P.-Y., Li, Q., Sato, A. I., Levy, D. E., Bromberg, J., Divino, C. M., Chen, S.-H. (2006). Gr-1+CD115+ Immature Myeloid Suppressor Cells Mediate the Development of Tumor-Induced T Regulatory Cells and T-Cell Anergy in Tumor-Bearing Host. Cancer Res. 66: 1123-1131 [Abstract] [Full Text]  
• Kang, S. S., Allen, P. M. (2005). Priming in the Presence of IL-10 Results in Direct Enhancement of CD8+ T Cell Primary Responses and Inhibition of Secondary Responses. J. Immunol. 174: 5382-5389 [Abstract] [Full Text]  
• Kuwata, H., Watanabe, Y., Miyoshi, H., Yamamoto, M., Kaisho, T., Takeda, K., Akira, S. (2003). IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-{alpha} production in macrophages. Blood 102: 4123-4129 [Abstract] [Full Text]  
• Lindsay, J O, Ciesielski, C J, Scheinin, T, Brennan, F M, Hodgson, H J (2003). Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis. Gut 52: 981-987 [Abstract] [Full Text]  
• Ben-Shlomo, I., Yu Hsu, S., Rauch, R., Kowalski, H. W., Hsueh, A. J. W. (2003). Signaling Receptome: A Genomic and Evolutionary Perspective of Plasma Membrane Receptors Involved in Signal Transduction. Sci Signal 2003: re9-re9 [Abstract] [Full Text]  
• Asadullah, K., Sterry, W., Volk, H. D. (2003). Interleukin-10 Therapy--Review of a New Approach. Pharmacol. Rev. 55: 241-269 [Abstract] [Full Text]  
• Gasche, C., Grundtner, P., Zwirn, P., Reinisch, W., Shaw, S. H., Zdanov, A., Sarma, U., Williams, L. M., Foxwell, B. M., Gangl, A. (2003). Novel Variants of the IL-10 Receptor 1 Affect Inhibition of Monocyte TNF-{alpha} Production. J. Immunol. 170: 5578-5582 [Abstract] [Full Text]  
• Niemand, C., Nimmesgern, A., Haan, S., Fischer, P., Schaper, F., Rossaint, R., Heinrich, P. C., Muller-Newen, G. (2003). Activation of STAT3 by IL-6 and IL-10 in Primary Human Macrophages Is Differentially Modulated by Suppressor of Cytokine Signaling 3. J. Immunol. 170: 3263-3272 [Abstract] [Full Text]  
• Lindsay, J O, Ciesielski, C J, Scheinin, T, Brennan, F M, Hodgson, H J (2003). Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis. Gut 52: 363-369 [Abstract] [Full Text]  
• Ding, Y., Chen, D., Tarcsafalvi, A., Su, R., Qin, L., Bromberg, J. S. (2003). Suppressor of Cytokine Signaling 1 Inhibits IL-10-Mediated Immune Responses. J. Immunol. 170: 1383-1391 [Abstract] [Full Text]  
• Cong, Y., Weaver, C. T., Lazenby, A., Elson, C. O. (2002). Bacterial-Reactive T Regulatory Cells Inhibit Pathogenic Immune Responses to the Enteric Flora. J. Immunol. 169: 6112-6119 [Abstract] [Full Text]  
• Mathurin, P., Xiong, S., Kharbanda, K. K., Veal, N., Miyahara, T., Motomura, K., Rippe, R. A., Bachem, M. G., Tsukamoto, H. (2002). IL-10 receptor and coreceptor expression in quiescent and activated hepatic stellate cells. Am. J. Physiol. Gastrointest. Liver Physiol. 282: G981-G990 [Abstract] [Full Text]  
• Ding, Y., Qin, L., Zamarin, D., Kotenko, S. V., Pestka, S., Moore, K. W., Bromberg, J. S. (2001). Differential IL-10R1 Expression Plays a Critical Role in IL-10-Mediated Immune Regulation. J. Immunol. 167: 6884-6892 [Abstract] [Full Text]  
• Zhou, J.-H., Broussard, S. R., Strle, K., Freund, G. G., Johnson, R. W., Dantzer, R., Kelley, K. W. (2001). IL-10 Inhibits Apoptosis of Promyeloid Cells by Activating Insulin Receptor Substrate-2 and Phosphatidylinositol 3'-Kinase. J. Immunol. 167: 4436-4442 [Abstract] [Full Text]  
• Avdiushko, R., Hongo, D., Lake-Bullock, H., Kaplan, A., Cohen, D. (2001). IL-10 receptor dysfunction in macrophages during chronic inflammation. J. Leukoc. Biol. 70: 624-632 [Abstract] [Full Text]  
• Frazer, K. A., Sheehan, J. B., Stokowski, R. P., Chen, X., Hosseini, R., Cheng, J.-F., Fodor, S. P.A., Cox, D. R., Patil, N. (2001). Evolutionarily Conserved Sequences on Human Chromosome 21. Genome Res 11: 1651-1659 [Abstract] [Full Text]  
• Crepaldi, L., Gasperini, S., Lapinet, J. A., Calzetti, F., Pinardi, C., Liu, Y., Zurawski, S., de Waal Malefyt, R., Moore, K. W., Cassatella, M. A. (2001). Up-Regulation of IL-10R1 Expression Is Required to Render Human Neutrophils Fully Responsive to IL-10. J. Immunol. 167: 2312-2322 [Abstract] [Full Text]  
• Tedgui, A., Mallat, Z. (2001). Anti-Inflammatory Mechanisms in the Vascular Wall. Circ. Res. 88: 877-887 [Abstract] [Full Text]  
• Elbim, C., Reglier, H., Fay, M., Delarche, C., Andrieu, V., El Benna, J., Gougerot-Pocidalo, M.-A. (2001). Intracellular Pool of IL-10 Receptors in Specific Granules of Human Neutrophils: Differential Mobilization by Proinflammatory Mediators. J. Immunol. 166: 5201-5207 [Abstract] [Full Text]  
• Corinti, S., Albanesi, C., la Sala, A., Pastore, S., Girolomoni, G. (2001). Regulatory Activity of Autocrine IL-10 on Dendritic Cell Functions. J. Immunol. 166: 4312-4318 [Abstract] [Full Text]  
• Dumoutier, L., Van Roost, E., Colau, D., Renauld, J.-C. (2000). Human interleukin-10-related T cell-derived inducible factor: Molecular cloning and functional characterization as an hepatocyte-stimulating factor. Proc. Natl. Acad. Sci. USA 10.1073/pnas.170291697v1 [Abstract] [Full Text]  
• Rennick, D. M., Fort, M. M. (2000). Lessons From Genetically Engineered Animal Models: XII. IL-10-deficient (IL-10-/-) mice and intestinal inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 278: G829-G833 [Abstract] [Full Text]  
• O'Farrell, A.-M., Parry, D. A., Zindy, F., Roussel, M. F., Lees, E., Moore, K. W., Mui, A. L.-F. (2000). Stat3-Dependent Induction of p19INK4D by IL-10 Contributes to Inhibition of Macrophage Proliferation. J. Immunol. 164: 4607-4615 [Abstract] [Full Text]  
• Josephson, K., DiGiacomo, R., Indelicato, S. R., Ayo, A. H., Nagabhushan, T. L., Parker, M. H., Walter, M. R. (2000). Design and Analysis of an Engineered Human Interleukin-10 Monomer. J. Biol. Chem. 275: 13552-13557 [Abstract] [Full Text]  
• BARNES, P. J. (2000). Endogenous Inhibitory Mechanisms in Asthma. Am. J. Respir. Crit. Care Med. 161: S176-181 [Full Text]  
• Denning, T. L., Campbell, N. A., Song, F., Garofalo, R. P., Klimpel, G. R., Reyes, V. E., Ernst, P. B. (2000). Expression of IL-10 receptors on epithelial cells from the murine small and large intestine. Int Immunol 12: 133-139 [Abstract] [Full Text]  
• Ding, Y., Qin, L., Kotenko, S. V., Pestka, S., Bromberg, J. S. (2000). A Single Amino Acid Determines the Immunostimulatory Activity of Interleukin 10. JEM 191: 213-224 [Abstract] [Full Text]  
• MacDonald, K. P. A., Pettit, A. R., Quinn, C., Thomas, G. J., Thomas, R. (1999). Resistance of Rheumatoid Synovial Dendritic Cells to the Immunosuppressive Effects of IL-10. J. Immunol. 163: 5599-5607 [Abstract] [Full Text]  
• Cassatella, M. A., Gasperini, S., Bovolenta, C., Calzetti, F., Vollebregt, M., Scapini, P., Marchi, M., Suzuki, R., Suzuki, A., Yoshimura, A. (1999). Interleukin-10 (IL-10) Selectively Enhances CIS3/SOCS3 mRNA Expression in Human Neutrophils: Evidence for an IL-10-Induced Pathway That Is Independent of STAT Protein Activation. Blood 94: 2880-2889 [Abstract] [Full Text]  
• Ryan, A. M. (1999). Commentary: Role of the Pathologist in the Identification and Characterization of Therapeutic Molecules. Toxicol Pathol 27: 474-476  
• Riley, J. K., Takeda, K., Akira, S., Schreiber, R. D. (1999). Interleukin-10 Receptor Signaling through the JAK-STAT Pathway. REQUIREMENT FOR TWO DISTINCT RECEPTOR-DERIVED SIGNALS FOR ANTI-INFLAMMATORY ACTION. J. Biol. Chem. 274: 16513-16521 [Abstract] [Full Text]  
• Reboul, J., Gardiner, K., Monneron, D., Uzé, G., Lutfalla, G. (1999). Comparative Genomic Analysis of the Interferon/Interleukin-10 Receptor Gene Cluster. Genome Res 9: 242-250 [Abstract] [Full Text]  
• Xie, M.-H., Aggarwal, S., Ho, W.-H., Foster, J., Zhang, Z., Stinson, J., Wood, W. I., Goddard, A. D., Gurney, A. L. (2000). Interleukin (IL)-22, a Novel Human Cytokine That Signals through the Interferon Receptor-related Proteins CRF2-4 and IL-22R. J. Biol. Chem. 275: 31335-31339 [Abstract] [Full Text]  
• Kotenko, S. V., Izotova, L. S., Mirochnitchenko, O. V., Esterova, E., Dickensheets, H., Donnelly, R. P., Pestka, S. (2001). Identification of the Functional Interleukin-22 (IL-22) Receptor Complex. THE IL-10R2 CHAIN (IL-10Rbeta ) IS A COMMON CHAIN OF BOTH THE IL-10 AND IL-22 (IL-10-RELATED T CELL-DERIVED INDUCIBLE FACTOR, IL-TIF) RECEPTOR COMPLEXES. J. Biol. Chem. 276: 2725-2732 [Abstract] [Full Text]  
• Dumoutier, L., Van Roost, E., Colau, D., Renauld, J.-C. (2000). Human interleukin-10-related T cell-derived inducible factor: Molecular cloning and functional characterization as an hepatocyte-stimulating factor. Proc. Natl. Acad. Sci. USA 97: 10144-10149 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS