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1 and a Novel Cytokine Receptor Subunit, IL-23R1
Departments of
* Immunology,
Molecular Biology, and
Molecular Pathology, DNAX Research, Palo Alto, CA 94304
IL-23 is a heterodimeric cytokine composed of the IL-12p40
"soluble receptor" subunit and a novel cytokine-like subunit
related to IL-12p35, termed p19. Human and mouse IL-23 exhibit some
activities similar to IL-12, but differ in their capacities to
stimulate particular populations of memory T cells. Like IL-12, IL-23
binds to the IL-12R subunit IL-12R
1. However, it does not use
IL-12R2. In this study, we identify a novel member of the
hemopoietin receptor family as a subunit of the receptor for IL-23,
"IL-23R." IL-23R pairs with IL-12R1 to confer IL-23
responsiveness on cells expressing both subunits. Human IL-23, but not
IL-12, exhibits detectable affinity for human IL-23R. Anti-IL-12R1
and anti-IL-23R Abs block IL-23 responses of an NK cell line and
Ba/F3 cells expressing the two receptor chains. IL-23 activates the
same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3,
-4, and -5, but stat4 activation is substantially weaker and different
DNA-binding stat complexes form in response to IL-23 compared with
IL-12. IL-23R associates constitutively with Jak2 and in a
ligand-dependent manner with stat3. The ability of cells to respond to
IL-23 or IL-12 correlates with expression of IL-23R or IL-12R2,
respectively. The human IL-23R gene is on human chromosome 1 within 150
kb of IL-12R2.
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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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E. Bettelli and V. K. Kuchroo IL-12- and IL-23-induced T helper cell subsets: birds of the same feather flock together J. Exp. Med., January 18, 2005; 201(2): 169 - 171. [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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D. Fairweather, S. Frisancho-Kiss, S. A. Yusung, M. A. Barrett, S. E. Davis, R. A. Steele, S. J. L. Gatewood, and N. R. Rose IL-12 Protects against Coxsackievirus B3-Induced Myocarditis by Increasing IFN-{gamma} and Macrophage and Neutrophil Populations in the Heart J. Immunol., January 1, 2005; 174(1): 261 - 269. [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 J O'Shea Targeting the Jak/STAT pathway for immunosuppression Ann Rheum Dis, November 1, 2004; 63(suppl_2): ii67 - ii71. [Full Text] [PDF]
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C. Fieschi, M. Bosticardo, L. de Beaucoudrey, S. Boisson-Dupuis, J. Feinberg, O. F. Santos, J. Bustamante, J. Levy, F. Candotti, and J.-L. Casanova A novel form of complete IL-12/IL-23 receptor {beta}1 deficiency with cell surface-expressed nonfunctional receptors Blood, October 1, 2004; 104(7): 2095 - 2101. [Abstract] [Full Text] [PDF]
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A. Morinobu, Y. Kanno, and J. J. O'Shea Discrete Roles for Histone Acetylation in Human T Helper 1 Cell-specific Gene Expression J. Biol. Chem., September 24, 2004; 279(39): 40640 - 40646. [Abstract] [Full Text] [PDF]
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S.-Z. Wang, Y.-X. Bao, C. L. Rosenberger, Y. Tesfaigzi, J. M. Stark, and K. S. Harrod IL-12p40 and IL-18 Modulate Inflammatory and Immune Responses to Respiratory Syncytial Virus Infection J. Immunol., September 15, 2004; 173(6): 4040 - 4049. [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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 J. Siren, T. Sareneva, J. Pirhonen, M. Strengell, V. Veckman, I. Julkunen, and S. Matikainen Cytokine and contact-dependent activation of natural killer cells by influenza A or Sendai virus-infected macrophages J. Gen. Virol., August 1, 2004; 85(8): 2357 - 2364. [Abstract] [Full Text] [PDF]
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L. Wassink, P. L. Vieira, H. H. Smits, G. A. Kingsbury, A. J. Coyle, M. L. Kapsenberg, and E. A. Wierenga ICOS Expression by Activated Human Th Cells Is Enhanced by IL-12 and IL-23: Increased ICOS Expression Enhances the Effector Function of Both Th1 and Th2 Cells J. Immunol., August 1, 2004; 173(3): 1779 - 1786. [Abstract] [Full Text] [PDF]
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L. A. Lieberman, F. Cardillo, A. M. Owyang, D. M. Rennick, D. J. Cua, R. A. Kastelein, and C. A. Hunter IL-23 Provides a Limited Mechanism of Resistance to Acute Toxoplasmosis in the Absence of IL-12 J. Immunol., August 1, 2004; 173(3): 1887 - 1893. [Abstract] [Full Text] [PDF]
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 L. S. Argetsinger, J.-L. K. Kouadio, H. Steen, A. Stensballe, O. N. Jensen, and C. Carter-Su Autophosphorylation of JAK2 on Tyrosines 221 and 570 Regulates Its Activity Mol. Cell. Biol., June 1, 2004; 24(11): 4955 - 4967. [Abstract] [Full Text] [PDF]
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R. J. Lund, Z. Chen, J. Scheinin, and R. Lahesmaa Early Target Genes of IL-12 and STAT4 Signaling in Th Cells J. Immunol., June 1, 2004; 172(11): 6775 - 6782. [Abstract] [Full Text] [PDF]
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K. A. Papadakis, J. L. Prehn, C. Landers, Q. Han, X. Luo, S. C. Cha, P. Wei, and S. R. Targan TL1A Synergizes with IL-12 and IL-18 to Enhance IFN-{gamma} Production in Human T Cells and NK Cells J. Immunol., June 1, 2004; 172(11): 7002 - 7007. [Abstract] [Full Text] [PDF]
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 L. A. Rosenthal, L. D. Mikus, A. Tuffaha, A. G. Mosser, R. L. Sorkness, and R. F. Lemanske Jr. Attenuated Innate Mechanisms of Interferon-{gamma} Production in Rats Susceptible to Postviral Airway Dysfunction Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 702 - 709. [Abstract] [Full Text] [PDF]
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A. Yamanaka, S. Hamano, Y. Miyazaki, K. Ishii, A. Takeda, T. W. Mak, K. Himeno, A. Yoshimura, and H. Yoshida Hyperproduction of Proinflammatory Cytokines by WSX-1-Deficient NKT Cells in Concanavalin A-Induced Hepatitis J. Immunol., March 15, 2004; 172(6): 3590 - 3596. [Abstract] [Full Text] [PDF]
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N. Ghilardi, N. Kljavin, Q. Chen, S. Lucas, A. L. Gurney, and F. J. de Sauvage Compromised Humoral and Delayed-Type Hypersensitivity Responses in IL-23-Deficient Mice J. Immunol., March 1, 2004; 172(5): 2827 - 2833. [Abstract] [Full Text] [PDF]
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E. Lee, W. L. Trepicchio, J. L. Oestreicher, D. Pittman, F. Wang, F. Chamian, M. Dhodapkar, and J. G. Krueger Increased Expression of Interleukin 23 p19 and p40 in Lesional Skin of Patients with Psoriasis Vulgaris J. Exp. Med., January 5, 2004; 199(1): 125 - 130. [Abstract] [Full Text] [PDF]
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S.-J. Ha, D.-J. Kim, K.-H. Baek, Y.-D. Yun, and Y.-C. Sung IL-23 Induces Stronger Sustained CTL and Th1 Immune Responses Than IL-12 in Hepatitis C Virus Envelope Protein 2 DNA Immunization J. Immunol., January 1, 2004; 172(1): 525 - 531. [Abstract] [Full Text] [PDF]
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C. A. Murphy, C. L. Langrish, Y. Chen, W. Blumenschein, T. McClanahan, R. A. Kastelein, J. D. Sedgwick, and D. J. Cua Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation J. Exp. Med., December 15, 2003; 198(12): 1951 - 1957. [Abstract] [Full Text] [PDF]
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T. D. Russell, Q. Yan, G. Fan, A. P. Khalifah, D. K. Bishop, S. L. Brody, and M. J. Walter IL-12 p40 Homodimer-Dependent Macrophage Chemotaxis and Respiratory Viral Inflammation Are Mediated through IL-12 Receptor {beta}1 J. Immunol., December 15, 2003; 171(12): 6866 - 6874. [Abstract] [Full Text] [PDF]
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C. Diveu, E. Lelievre, D. Perret, A.-H. L. Lak-Hal, J. Froger, C. Guillet, S. Chevalier, F. Rousseau, A. Wesa, L. Preisser, et al. GPL, a Novel Cytokine Receptor Related to GP130 and Leukemia Inhibitory Factor Receptor J. Biol. Chem., December 12, 2003; 278(50): 49850 - 49859. [Abstract] [Full Text] [PDF]
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