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DNAX Research Institute, Palo Alto, CA 94304
The recently discovered cytokine IL-27 belongs to the IL-6/IL-12 family of cytokines and induced proliferation of naive CD4+ T cells and the generation of a Th1-type adaptive immune response. Although binding of IL-27 to the cytokine receptor WSX-1 was demonstrated, this interaction proved insufficient to mediate cellular effects. Hence, IL-27 was believed to form a heteromeric signaling receptor complex with WSX-1 and another, yet to be identified, cytokine receptor subunit. In this study, we describe that WSX-1 together with gp130 constitutes a functional signal-transducing receptor for IL-27. We show that neither of the two subunits itself is sufficient to mediate IL-27-induced signal transduction, but that the combination of both is required for this event. Expression analysis of WSX-1 and gp130 by quantitative PCR suggests that IL-27 might have a variety of cellular targets besides naive CD4+ T cells: we demonstrate gene induction of a subset of inflammatory cytokines in primary human mast cells and monocytes in response to IL-27 stimulation. Thus, IL-27 not only contributes to the development of an adaptive immune response through its action on CD4+ T cells, it also directly acts on cells of the innate immune system.
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 N Sugiyama, H Nakashima, T Yoshimura, A Sadanaga, S Shimizu, K Masutani, T Igawa, M Akahoshi, K Miyake, A Takeda, et al. Amelioration of human lupus-like phenotypes in MRL/lpr mice by overexpression of interleukin 27 receptor {alpha} (WSX-1) Ann Rheum Dis, October 1, 2008; 67(10): 1461 - 1467. [Abstract] [Full Text] [PDF]
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C. Hintzen, C. Evers, B. E. Lippok, R. Volkmer, P. C. Heinrich, S. Radtke, and H. M. Hermanns Box 2 Region of the Oncostatin M Receptor Determines Specificity for Recruitment of Janus Kinases and STAT5 Activation J. Biol. Chem., July 11, 2008; 283(28): 19465 - 19477. [Abstract] [Full Text] [PDF]
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 A. V. Villarino, D. Artis, J. S. Bezbradica, O. Miller, C. J. M. Saris, S. Joyce, and C. A. Hunter IL-27R deficiency delays the onset of colitis and protects from helminth-induced pathology in a model of chronic IBD Int. Immunol., June 1, 2008; 20(6): 739 - 752. [Abstract] [Full Text] [PDF]
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G. D. Kalliolias and L. B. Ivashkiv IL-27 Activates Human Monocytes via STAT1 and Suppresses IL-10 Production but the Inflammatory Functions of IL-27 Are Abrogated by TLRs and p38 J. Immunol., May 1, 2008; 180(9): 6325 - 6333. [Abstract] [Full Text] [PDF]
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M. Batten, N. M. Kljavin, J. Li, M. J. Walter, F. J. de Sauvage, and N. Ghilardi Cutting Edge: IL-27 Is a Potent Inducer of IL-10 but Not FoxP3 in Murine T Cells J. Immunol., March 1, 2008; 180(5): 2752 - 2756. [Abstract] [Full Text] [PDF]
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T. Owaki, M. Asakawa, N. Morishima, I. Mizoguchi, F. Fukai, K. Takeda, J. Mizuguchi, and T. Yoshimoto STAT3 Is Indispensable to IL-27-Mediated Cell Proliferation but Not to IL-27-Induced Th1 Differentiation and Suppression of Proinflammatory Cytokine Production J. Immunol., March 1, 2008; 180(5): 2903 - 2911. [Abstract] [Full Text] [PDF]
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 J. Seita, M. Asakawa, J. Ooehara, S.-i. Takayanagi, Y. Morita, N. Watanabe, K. Fujita, M. Kudo, J. Mizuguchi, H. Ema, et al. Interleukin-27 directly induces differentiation in hematopoietic stem cells Blood, February 15, 2008; 111(4): 1903 - 1912. [Abstract] [Full Text] [PDF]
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M. Huber, V. Steinwald, A. Guralnik, A. Brustle, P. Kleemann, C. Rosenplanter, T. Decker, and M. Lohoff IL-27 inhibits the development of regulatory T cells via STAT3 Int. Immunol., February 1, 2008; 20(2): 223 - 234. [Abstract] [Full Text] [PDF]
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 A. Pradhan, Q. T. Lambert, and G. W. Reuther Transformation of hematopoietic cells and activation of JAK2-V617F by IL-27R, a component of a heterodimeric type I cytokine receptor PNAS, November 20, 2007; 104(47): 18502 - 18507. [Abstract] [Full Text] [PDF]
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S. Wang, Y. Miyazaki, Y. Shinozaki, and H. Yoshida Augmentation of Antigen-Presenting and Th1-Promoting Functions of Dendritic Cells by WSX-1(IL-27R) Deficiency J. Immunol., November 15, 2007; 179(10): 6421 - 6428. [Abstract] [Full Text] [PDF]
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M. F Neurath New therapies for sepsis: focus on the interleukin (IL)12 family member IL27 Ann Rheum Dis, November 1, 2007; 66(suppl_3): iii29 - iii31. [Abstract] [Full Text] [PDF]
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T. Yoshimoto, T. Yoshimoto, K. Yasuda, J. Mizuguchi, and K. Nakanishi IL-27 Suppresses Th2 Cell Development and Th2 Cytokines Production from Polarized Th2 Cells: A Novel Therapeutic Way for Th2-Mediated Allergic Inflammation J. Immunol., October 1, 2007; 179(7): 4415 - 4423. [Abstract] [Full Text] [PDF]
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C. Brender, G. M. Tannahill, B. J. Jenkins, J. Fletcher, R. Columbus, C. J. M. Saris, M. Ernst, N. A. Nicola, D. J. Hilton, W. S. Alexander, et al. Suppressor of cytokine signaling 3 regulates CD8 T-cell proliferation by inhibition of interleukins 6 and 27 Blood, October 1, 2007; 110(7): 2528 - 2536. [Abstract] [Full Text] [PDF]
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D. C. Fitzgerald, B. Ciric, T. Touil, H. Harle, J. Grammatikopolou, J. D. Sarma, B. Gran, G.-X. Zhang, and A. Rostami Suppressive Effect of IL-27 on Encephalitogenic Th17 Cells and the Effector Phase of Experimental Autoimmune Encephalomyelitis J. Immunol., September 1, 2007; 179(5): 3268 - 3275. [Abstract] [Full Text] [PDF]
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J. M. Fakruddin, R. A. Lempicki, R. J. Gorelick, J. Yang, J. W. Adelsberger, A. J. Garcia-Pineres, L. A. Pinto, H. C. Lane, and T. Imamichi Noninfectious papilloma virus-like particles inhibit HIV-1 replication: implications for immune control of HIV-1 infection by IL-27 Blood, March 1, 2007; 109(5): 1841 - 1849. [Abstract] [Full Text] [PDF]
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C. Diveu, E. Venereau, J. Froger, E. Ravon, L. Grimaud, F. Rousseau, S. Chevalier, and H. Gascan Molecular and Functional Characterization of a Soluble Form of Oncostatin M/Interleukin-31 Shared Receptor J. Biol. Chem., December 1, 2006; 281(48): 36673 - 36682. [Abstract] [Full Text] [PDF]
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T. Owaki, M. Asakawa, F. Fukai, J. Mizuguchi, and T. Yoshimoto IL-27 Induces Th1 Differentiation via p38 MAPK/T-bet- and Intercellular Adhesion Molecule-1/LFA-1/ERK1/2-Dependent Pathways J. Immunol., December 1, 2006; 177(11): 7579 - 7587. [Abstract] [Full Text] [PDF]
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T. Yoshimura, A. Takeda, S. Hamano, Y. Miyazaki, I. Kinjyo, T. Ishibashi, A. Yoshimura, and H. Yoshida Two-Sided Roles of IL-27: Induction of Th1 Differentiation on Naive CD4+ T Cells versus Suppression of Proinflammatory Cytokine Production Including IL-23-Induced IL-17 on Activated CD4+ T Cells Partially Through STAT3-Dependent Mechanism J. Immunol., October 15, 2006; 177(8): 5377 - 5385. [Abstract] [Full Text] [PDF]
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M. Kovaleva, I. Bussmeyer, B. Rabe, J. Grotzinger, E. Sudarman, J. Eichler, U. Conrad, S. Rose-John, and J. Scheller Abrogation of Viral Interleukin-6 (vIL-6)-Induced Signaling by Intracellular Retention and Neutralization of vIL-6 with an Anti-vIL-6 Single-Chain Antibody Selected by Phage Display. J. Virol., September 1, 2006; 80(17): 8510 - 8520. [Abstract] [Full Text] [PDF]
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 S. Wirtz, I. Tubbe, P. R. Galle, H. J. Schild, M. Birkenbach, R. S. Blumberg, and M. F. Neurath Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27 J. Exp. Med., August 7, 2006; 203(8): 1875 - 1881. [Abstract] [Full Text] [PDF]
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 S. Rose-John, J. Scheller, G. Elson, and S. A. Jones Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer J. Leukoc. Biol., August 1, 2006; 80(2): 227 - 236. [Abstract] [Full Text] [PDF]
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C. Stuhlmann-Laeisz, S. Lang, A. Chalaris, P. Krzysztof, S. Enge, J. Eichler, U. Klingmuller, M. Samuel, M. Ernst, S. Rose-John, et al. Forced Dimerization of gp130 Leads to Constitutive STAT3 Activation, Cytokine-independent Growth, and Blockade of Differentiation of Embryonic Stem Cells Mol. Biol. Cell, July 1, 2006; 17(7): 2986 - 2995. [Abstract] [Full Text] [PDF]
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S. Oniki, H. Nagai, T. Horikawa, J. Furukawa, M. L. Belladonna, T. Yoshimoto, I. Hara, and C. Nishigori Interleukin-23 and interleukin-27 exert quite different antitumor and vaccine effects on poorly immunogenic melanoma. Cancer Res., June 15, 2006; 66(12): 6395 - 6404. [Abstract] [Full Text] [PDF]
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M. Shimizu, M. Shimamura, T. Owaki, M. Asakawa, K. Fujita, M. Kudo, Y. Iwakura, Y. Takeda, A. D. Luster, J. Mizuguchi, et al. Antiangiogenic and Antitumor Activities of IL-27. J. Immunol., June 15, 2006; 176(12): 7317 - 7324. [Abstract] [Full Text] [PDF]
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F. Larousserie, P. Charlot, E. Bardel, J. Froger, R. A. Kastelein, and O. Devergne Differential Effects of IL-27 on Human B Cell Subsets J. Immunol., May 15, 2006; 176(10): 5890 - 5897. [Abstract] [Full Text] [PDF]
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C. Stross, S. Radtke, T. Clahsen, C. Gerlach, R. Volkmer-Engert, F. Schaper, P. C. Heinrich, and H. M. Hermanns Oncostatin M Receptor-mediated Signal Transduction Is Negatively Regulated by SOCS3 through a Receptor Tyrosine-independent Mechanism J. Biol. Chem., March 31, 2006; 281(13): 8458 - 8468. [Abstract] [Full Text] [PDF]
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T. Owaki, M. Asakawa, S. Kamiya, K. Takeda, F. Fukai, J. Mizuguchi, and T. Yoshimoto IL-27 Suppresses CD28-Medicated IL-2 Production through Suppressor of Cytokine Signaling 3. J. Immunol., March 1, 2006; 176(5): 2773 - 2780. [Abstract] [Full Text] [PDF]
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S. Radtke, A. Jorissen, H. S.-V. de Leur, P. C. Heinrich, and I. Behrmann Three Dileucine-like Motifs within the Interbox1/2 Region of the Human Oncostatin M Receptor Prevent Efficient Surface Expression in the Absence of an Associated Janus Kinase J. Biol. Chem., February 17, 2006; 281(7): 4024 - 4034. [Abstract] [Full Text] [PDF]
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A. V. Villarino, J. S. Stumhofer, C. J. M. Saris, R. A. Kastelein, F. J. de Sauvage, and C. A. Hunter IL-27 Limits IL-2 Production during Th1 Differentiation J. Immunol., January 1, 2006; 176(1): 237 - 247. [Abstract] [Full Text] [PDF]
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 L. E. Rosas, A. A. Satoskar, K. M. Roth, T. L. Keiser, J. Barbi, C. Hunter, F. J. de Sauvage, and A. R. Satoskar Interleukin-27R (WSX-1/T-Cell Cytokine Receptor) Gene-Deficient Mice Display Enhanced Resistance to Leishmania donovani Infection but Develop Severe Liver Immunopathology Am. J. Pathol., January 1, 2006; 168(1): 158 - 169. [Abstract] [Full Text] [PDF]
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T. Owaki, M. Asakawa, N. Morishima, K. Hata, F. Fukai, M. Matsui, J. Mizuguchi, and T. Yoshimoto A Role for IL-27 in Early Regulation of Th1 Differentiation J. Immunol., August 15, 2005; 175(4): 2191 - 2200. [Abstract] [Full Text] [PDF]
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N. Morishima, T. Owaki, M. Asakawa, S. Kamiya, J. Mizuguchi, and T. Yoshimoto Augmentation of Effector CD8+ T Cell Generation with Enhanced Granzyme B Expression by IL-27 J. Immunol., August 1, 2005; 175(3): 1686 - 1693. [Abstract] [Full Text] [PDF]
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A. Takeda, S. Hamano, H. Shiraishi, T. Yoshimura, H. Ogata, K. Ishii, T. Ishibashi, A. Yoshimura, and H. Yoshida WSX-1 over-expression in CD4+ T cells leads to hyperproliferation and cytokine hyperproduction in response to TCR stimulation Int. Immunol., July 1, 2005; 17(7): 889 - 897. [Abstract] [Full Text] [PDF]
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A. V. Villarino, J. Larkin III, C. J. M. Saris, A. J. Caton, S. Lucas, T. Wong, F. J. de Sauvage, and C. A. Hunter Positive and Negative Regulation of the IL-27 Receptor during Lymphoid Cell Activation J. Immunol., June 15, 2005; 174(12): 7684 - 7691. [Abstract] [Full Text] [PDF]
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F. Larousserie, E. Bardel, S. Pflanz, B. Arnulf, C. Lome-Maldonado, O. Hermine, L. Bregeaud, M. Perennec, N. Brousse, R. Kastelein, et al. Analysis of Interleukin-27 (EBI3/p28) Expression in Epstein-Barr Virus- and Human T-Cell Leukemia Virus Type 1-Associated Lymphomas: Heterogeneous Expression of EBI3 Subunit by Tumoral Cells Am. J. Pathol., April 1, 2005; 166(4): 1217 - 1228. [Abstract] [Full Text] [PDF]
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C. Holscher, A. Holscher, D. Ruckerl, T. Yoshimoto, H. Yoshida, T. Mak, C. Saris, and S. Ehlers The IL-27 Receptor Chain WSX-1 Differentially Regulates Antibacterial Immunity and Survival during Experimental Tuberculosis J. Immunol., March 15, 2005; 174(6): 3534 - 3544. [Abstract] [Full Text] [PDF]
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S. Wirtz, C. Becker, M. C. Fantini, E. E. Nieuwenhuis, I. Tubbe, P. R. Galle, H.-J. Schild, M. Birkenbach, R. S. Blumberg, and M. F. Neurath EBV-Induced Gene 3 Transcription Is Induced by TLR Signaling in Primary Dendritic Cells via NF-{kappa}B Activation J. Immunol., March 1, 2005; 174(5): 2814 - 2824. [Abstract] [Full Text] [PDF]
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M. Schnurr, T. Toy, A. Shin, M. Wagner, J. Cebon, and E. Maraskovsky Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway Blood, February 15, 2005; 105(4): 1582 - 1589. [Abstract] [Full Text] [PDF]
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J. Sun, M. Walsh, A. V. Villarino, L. Cervi, C. A. Hunter, Y. Choi, and E. J. Pearce TLR Ligands Can Activate Dendritic Cells to Provide a MyD88-Dependent Negative Signal for Th2 Cell Development J. Immunol., January 15, 2005; 174(2): 742 - 751. [Abstract] [Full Text] [PDF]
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R. Salcedo, J. K. Stauffer, E. Lincoln, T. C. Back, J. A. Hixon, C. Hahn, K. Shafer-Weaver, A. Malyguine, R. Kastelein, and J. M. Wigginton IL-27 Mediates Complete Regression of Orthotopic Primary and Metastatic Murine Neuroblastoma Tumors: Role for CD8+ T Cells J. Immunol., December 15, 2004; 173(12): 7170 - 7182. [Abstract] [Full Text] [PDF]
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J. E. Pearl, S. A. Khader, A. Solache, L. Gilmartin, N. Ghilardi, F. deSauvage, and A. M. Cooper IL-27 Signaling Compromises Control of Bacterial Growth in Mycobacteria-Infected Mice J. Immunol., December 15, 2004; 173(12): 7490 - 7496. [Abstract] [Full Text] [PDF]
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D. Artis, A. Villarino, M. Silverman, W. He, E. M. Thornton, S. Mu, S. Summer, T. M. Covey, E. Huang, H. Yoshida, et al. The IL-27 Receptor (WSX-1) Is an Inhibitor of Innate and Adaptive Elements of Type 2 Immunity J. Immunol., November 1, 2004; 173(9): 5626 - 5634. [Abstract] [Full Text] [PDF]
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 U. von Rango, J. Alfer, S. Kertschanska, B. Kemp, G. Muller-Newen, P.C. Heinrich, H.M. Beier, and I. Classen-Linke Interleukin-11 expression: its significance in eutopic and ectopic human implantation Mol. Hum. Reprod., November 1, 2004; 10(11): 783 - 792. [Abstract] [Full Text] [PDF]
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D. Perret, C. Guillet, G. Elson, J. Froger, H. Plun-Favreau, F. Rousseau, M. Chabbert, J.-F. Gauchat, and H. Gascan Two Different Contact Sites Are Recruited by Cardiotrophin-like Cytokine (CLC) to Generate the CLC/CLF and CLC/sCNTFR{alpha} Composite Cytokines J. Biol. Chem., October 15, 2004; 279(42): 43961 - 43970. [Abstract] [Full Text] [PDF]
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S. Kamiya, T. Owaki, N. Morishima, F. Fukai, J. Mizuguchi, and T. Yoshimoto An Indispensable Role for STAT1 in IL-27-Induced T-bet Expression but Not Proliferation of Naive CD4+ T Cells J. Immunol., September 15, 2004; 173(6): 3871 - 3877. [Abstract] [Full Text] [PDF]
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M. Matsui, O. Moriya, M. L. Belladonna, S. Kamiya, F. A. Lemonnier, T. Yoshimoto, and T. Akatsuka Adjuvant Activities of Novel Cytokines, Interleukin-23 (IL-23) and IL-27, for Induction of Hepatitis C Virus-Specific Cytotoxic T Lymphocytes in HLA-A*0201 Transgenic Mice J. Virol., September 1, 2004; 78(17): 9093 - 9104. [Abstract] [Full Text] [PDF]
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A. V. Villarino, E. Huang, and C. A. Hunter Understanding the Pro- and Anti-Inflammatory Properties of IL-27 J. Immunol., July 15, 2004; 173(2): 715 - 720. [Abstract] [Full Text] [PDF]
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