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*
Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033;
Department of Drug Safety and Metabolism, Schering-Plough Research Institute, Lafayette, NJ 07848; and
DNAX Research Institute, Palo Alto, CA 94304
p19, a molecule structurally related to IL-6, G-CSF, and the p35
subunit of IL-12, is a subunit of the recently discovered cytokine
IL-23. Here we show that expression of p19 in multiple tissues of
transgenic mice induced a striking phenotype characterized by runting,
systemic inflammation, infertility, and death before 3 mo of age.
Founder animals had infiltrates of lymphocytes and macrophages in skin,
lung, liver, pancreas, and the digestive tract and were anemic. The
serum concentrations of the proinflammatory cytokines TNF-
and IL-1
were elevated, and the number of circulating neutrophils was increased.
In addition, ubiquitous expression of p19 resulted in constitutive
expression of acute phase proteins in the liver. Surprisingly,
liver-specific expression of p19 failed to reproduce any of these
abnormalities, suggesting specific requirements for production of
biologically active p19. Bone marrow transfer experiments showed that
expression of p19 by hemopoietic cells alone recapitulated the
phenotype induced by its widespread expression, pointing to hemopoietic
cells as the source of biologically active p19. These findings indicate
that p19 shares biological properties with IL-6, IL-12, and G-CSF and
that cell-specific expression is required for its biological
activity.
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 S. Aggarwal, N. Ghilardi, M.-H. Xie, F. J. de Sauvage, and A. L. Gurney Interleukin-23 Promotes a Distinct CD4 T Cell Activation State Characterized by the Production of Interleukin-17 J. Biol. Chem., January 10, 2003; 278(3): 1910 - 1914. [Abstract] [Full Text] [PDF]
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C. S. R. Lankford and D. M. Frucht A unique role for IL-23 in promoting cellular immunity J. Leukoc. Biol., January 1, 2003; 73(1): 49 - 56. [Abstract] [Full Text] [PDF]
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B. Gran, G.-X. Zhang, S. Yu, J. Li, X.-H. Chen, E. S. Ventura, M. Kamoun, and A. Rostami IL-12p35-Deficient Mice Are Susceptible to Experimental Autoimmune Encephalomyelitis: Evidence for Redundancy in the IL-12 System in the Induction of Central Nervous System Autoimmune Demyelination J. Immunol., December 15, 2002; 169(12): 7104 - 7110. [Abstract] [Full Text] [PDF]
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J. Pirhonen, S. Matikainen, and I. Julkunen Regulation of Virus-Induced IL-12 and IL-23 Expression in Human Macrophages J. Immunol., November 15, 2002; 169(10): 5673 - 5678. [Abstract] [Full Text] [PDF]
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M. L. Belladonna, J.-C. Renauld, R. Bianchi, C. Vacca, F. Fallarino, C. Orabona, M. C. Fioretti, U. Grohmann, and P. Puccetti IL-23 and IL-12 Have Overlapping, but Distinct, Effects on Murine Dendritic Cells J. Immunol., June 1, 2002; 168(11): 5448 - 5454. [Abstract] [Full Text] [PDF]
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C. Parham, M. Chirica, J. Timans, E. Vaisberg, M. Travis, J. Cheung, S. Pflanz, R. Zhang, K. P. Singh, F. Vega, et al. A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12R{beta}1 and a Novel Cytokine Receptor Subunit, IL-23R J. Immunol., June 1, 2002; 168(11): 5699 - 5708. [Abstract] [Full Text] [PDF]
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K. R. B. Bastos, J. M. Alvarez, C. R. F. Marinho, L. V. Rizzo, and M. R. D'Imperio Lima Macrophages from IL-12p40-deficient mice have a bias toward the M2 activation profile J. Leukoc. Biol., February 1, 2002; 71(2): 271 - 278. [Abstract] [Full Text] [PDF]
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 D. M. Frucht IL-23: A Cytokine That Acts on Memory T Cells Sci. Signal., January 8, 2002; 2002(114): pe1 - pe1. [Abstract] [Full Text] [PDF]
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