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¹ Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
² Experimental Pathology and Pharmacology, DNAX Research Inc., Palo Alto, CA 94304
³ Bioinformatics, DNAX Research Inc., Palo Alto, CA 94304

CORRESPONDENCE Daniel J. Cua: daniel.cua{at}dnax.org

Interleukin (IL)-23 is a heterodimeric cytokine composed of a unique p19 subunit, and a common p40 subunit shared with IL-12. IL-12 is important for the development of T helper (Th)1 cells that are essential for host defense and tumor suppression. In contrast, IL-23 does not promote the development of interferon-–producing Th1 cells, but is one of the essential factors required for the expansion of a pathogenic CD4⁺ T cell population, which is characterized by the production of IL-17, IL-17F, IL-6, and tumor necrosis factor. Gene expression analysis of IL-23–driven autoreactive T cells identified a unique expression pattern of proinflammatory cytokines and other novel factors, distinguishing them from IL-12–driven T cells. Using passive transfer studies, we confirm that these IL-23–dependent CD4⁺ T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity.

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• Chizzolini, C., Chicheportiche, R., Alvarez, M., de Rham, C., Roux-Lombard, P., Ferrari-Lacraz, S., Dayer, J.-M. (2008). Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion. Blood 112: 3696-3703 [Abstract] [Full Text]  
• Fabis, M. J., Phares, T. W., Kean, R. B., Koprowski, H., Hooper, D. C. (2008). Blood-brain barrier changes and cell invasion differ between therapeutic immune clearance of neurotrophic virus and CNS autoimmunity. Proc. Natl. Acad. Sci. USA 105: 15511-15516 [Abstract] [Full Text]  
• Miyahara, Y., Odunsi, K., Chen, W., Peng, G., Matsuzaki, J., Wang, R.-F. (2008). Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer. Proc. Natl. Acad. Sci. USA 105: 15505-15510 [Abstract] [Full Text]  
• Webb, A., Johnson, A., Fortunato, M., Platt, A., Crabbe, T., Christie, M. I., Watt, G. F., Ward, S. G., Jopling, L. A. (2008). Evidence for PI-3K-dependent migration of Th17-polarized cells in response to CCR2 and CCR6 agonists. J. Leukoc. Biol. 84: 1202-1212 [Abstract] [Full Text]  
• Rowan, A. G., Fletcher, J. M., Ryan, E. J., Moran, B., Hegarty, J. E., O'Farrelly, C., Mills, K. H. G. (2008). Hepatitis C Virus-Specific Th17 Cells Are Suppressed by Virus-Induced TGF-{beta}. J. Immunol. 181: 4485-4494 [Abstract] [Full Text]  
• Al-Salleeh, F., Petro, T. M. (2008). Promoter Analysis Reveals Critical Roles for SMAD-3 and ATF-2 in Expression of IL-23 p19 in Macrophages. J. Immunol. 181: 4523-4533 [Abstract] [Full Text]  
• Kryczek, I., Bruce, A. T., Gudjonsson, J. E., Johnston, A., Aphale, A., Vatan, L., Szeliga, W., Wang, Y., Liu, Y., Welling, T. H., Elder, J. T., Zou, W. (2008). Induction of IL-17+ T Cell Trafficking and Development by IFN-{gamma}: Mechanism and Pathological Relevance in Psoriasis. J. Immunol. 181: 4733-4741 [Abstract] [Full Text]  
• Roses, R. E., Xu, S., Xu, M., Koldovsky, U., Koski, G., Czerniecki, B. J. (2008). Differential Production of IL-23 and IL-12 by Myeloid-Derived Dendritic Cells in Response to TLR Agonists. J. Immunol. 181: 5120-5127 [Abstract] [Full Text]  
• Li, Z., Liu, B., Maminishkis, A., Mahesh, S. P., Yeh, S., Lew, J., Lim, W. K., Sen, H. N., Clarke, G., Buggage, R., Miller, S. S., Nussenblatt, R. B. (2008). Gene Expression Profiling in Autoimmune Noninfectious Uveitis Disease. J. Immunol. 181: 5147-5157 [Abstract] [Full Text]  
• Tsutsui, S., Hahn, J. N., Johnson, T. A., Ali, Z., Jirik, F. R. (2008). Absence of the Cellular Prion Protein Exacerbates and Prolongs Neuroinflammation in Experimental Autoimmune Encephalomyelitis. Am. J. Pathol. 173: 1029-1041 [Abstract] [Full Text]  

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