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Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
IL-17 is a proinflammatory cytokine that activates T cells and other immune cells to produce a variety of cytokines, chemokines, and cell adhesion molecules. This cytokine is augmented in the sera and/or tissues of patients with contact dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL-17 is involved in the development of autoimmune arthritis and contact, delayed, and airway hypersensitivity in mice. As the expression of IL-17 is also augmented in multiple sclerosis, we examined the involvement of this cytokine in these diseases using IL-17–/– murine disease models. We found that the development of experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis, was significantly suppressed in IL-17–/– mice; these animals exhibited delayed onset, reduced maximum severity scores, ameliorated histological changes, and early recovery. T cell sensitization against myelin oligodendrocyte glycoprotein was reduced in IL-17–/– mice upon sensitization. The major producer of IL-17 upon treatment with myelin digodendrocyte glycopritein was CD4+ T cells rather than CD8+ T cells, and adoptive transfer of IL-17–/– CD4+ T cells inefficiently induced EAE in recipient mice. Notably, IL-17-producing T cells were increased in IFN-
–/– cells, while IFN--producing cells were increased in IL-17–/– cells, suggesting that IL-17 and IFN- mutually regulate IFN- and IL-17 production. These observations indicate that IL-17 rather than IFN- plays a crucial role in the development of EAE.
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S. Wilkie, G. Picco, J. Foster, D. M. Davies, S. Julien, L. Cooper, S. Arif, S. J. Mather, J. Taylor-Papadimitriou, J. M. Burchell, et al. Retargeting of Human T Cells to Tumor-Associated MUC1: The Evolution of a Chimeric Antigen Receptor J. Immunol., April 1, 2008; 180(7): 4901 - 4909. [Abstract] [Full Text] [PDF]
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 I. Ifergan, H. Kebir, M. Bernard, K. Wosik, A. Dodelet-Devillers, R. Cayrol, N. Arbour, and A. Prat The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells Brain, March 1, 2008; 131(3): 785 - 799. [Abstract] [Full Text] [PDF]
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S. J. Molesworth-Kenyon, R. Yin, J. E. Oakes, and R. N. Lausch IL-17 receptor signaling influences virus-induced corneal inflammation J. Leukoc. Biol., February 1, 2008; 83(2): 401 - 408. [Abstract] [Full Text] [PDF]
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T. Yoshimura, K.-H. Sonoda, Y. Miyazaki, Y. Iwakura, T. Ishibashi, A. Yoshimura, and H. Yoshida Differential roles for IFN-{gamma} and IL-17 in experimental autoimmune uveoretinitis Int. Immunol., February 1, 2008; 20(2): 209 - 214. [Abstract] [Full Text] [PDF]
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Y. Cao, P. D. Doodes, T. T. Glant, and A. Finnegan IL-27 Induces a Th1 Immune Response and Susceptibility to Experimental Arthritis J. Immunol., January 15, 2008; 180(2): 922 - 930. [Abstract] [Full Text] [PDF]
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H. W. Lim, J. Lee, P. Hillsamer, and C. H. Kim Human Th17 Cells Share Major Trafficking Receptors with Both Polarized Effector T Cells and FOXP3+ Regulatory T Cells J. Immunol., January 1, 2008; 180(1): 122 - 129. [Abstract] [Full Text] [PDF]
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R. Gold and F. Luhder Interleukin-17--Extended Features of a Key Player in Multiple Sclerosis Am. J. Pathol., January 1, 2008; 172(1): 8 - 10. [Abstract] [Full Text] [PDF]
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J. S. Tzartos, M. A. Friese, M. J. Craner, J. Palace, J. Newcombe, M. M. Esiri, and L. Fugger Interleukin-17 Production in Central Nervous System-Infiltrating T Cells and Glial Cells Is Associated with Active Disease in Multiple Sclerosis Am. J. Pathol., January 1, 2008; 172(1): 146 - 155. [Abstract] [Full Text] [PDF]
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L. C. Zaba, I. Cardinale, P. Gilleaudeau, M. Sullivan-Whalen, M. Suarez-Farinas, J. Fuentes-Duculan, I. Novitskaya, A. Khatcherian, M. J. Bluth, M. A. Lowes, et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses J. Exp. Med., December 24, 2007; 204(13): 3183 - 3194. [Abstract] [Full Text] [PDF]
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K. Kreymborg, R. Etzensperger, L. Dumoutier, S. Haak, A. Rebollo, T. Buch, F. L. Heppner, J.-C. Renauld, and B. Becher IL-22 Is Expressed by Th17 Cells in an IL-23-Dependent Fashion, but Not Required for the Development of Autoimmune Encephalomyelitis J. Immunol., December 15, 2007; 179(12): 8098 - 8104. [Abstract] [Full Text] [PDF]
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D. Noguchi, D. Wakita, M. Tajima, S. Ashino, Y. Iwakura, Y. Zhang, K. Chamoto, H. Kitamura, and T. Nishimura Blocking of IL-6 signaling pathway prevents CD4+ T cell-mediated colitis in a Th17-independent manner Int. Immunol., December 1, 2007; 19(12): 1431 - 1440. [Abstract] [Full Text] [PDF]
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J. Moisan, R. Grenningloh, E. Bettelli, M. Oukka, and I-C. Ho Ets-1 is a negative regulator of Th17 differentiation J. Exp. Med., November 26, 2007; 204(12): 2825 - 2835. [Abstract] [Full Text] [PDF]
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X. Chen, S. Vodanovic-Jankovic, B. Johnson, M. Keller, R. Komorowski, and W. R. Drobyski Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versus-host disease Blood, November 15, 2007; 110(10): 3804 - 3813. [Abstract] [Full Text] [PDF]
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 S. Sinha, S. Subramanian, T. M. Proctor, L. J. Kaler, M. Grafe, R. Dahan, J. Huan, A. A. Vandenbark, G. G. Burrows, and H. Offner A Promising Therapeutic Approach for Multiple Sclerosis: Recombinant T-Cell Receptor Ligands Modulate Experimental Autoimmune Encephalomyelitis by Reducing Interleukin-17 Production and Inhibiting Migration of Encephalitogenic Cells into the CNS J. Neurosci., November 14, 2007; 27(46): 12531 - 12539. [Abstract] [Full Text] [PDF]
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M. Oukka Interplay between pathogenic Th17 and regulatory T cells Ann Rheum Dis, November 1, 2007; 66(suppl_3): iii87 - iii90. [Abstract] [Full Text] [PDF]
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S. Kohyama, S. Ohno, A. Isoda, O. Moriya, M. L. Belladonna, H. Hayashi, Y. Iwakura, T. Yoshimoto, T. Akatsuka, and M. Matsui IL-23 Enhances Host Defense against Vaccinia Virus Infection Via a Mechanism Partly Involving IL-17 J. Immunol., September 15, 2007; 179(6): 3917 - 3925. [Abstract] [Full Text] [PDF]
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 Y. Peng, G. Han, H. Shao, Y. Wang, H. J. Kaplan, and D. Sun Characterization of IL-17+ Interphotoreceptor Retinoid-Binding Protein-Specific T Cells in Experimental Autoimmune Uveitis Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4153 - 4161. [Abstract] [Full Text] [PDF]
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M. Muller, S. L. Carter, M. J. Hofer, P. Manders, D. R. Getts, M. T. Getts, A. Dreykluft, B. Lu, C. Gerard, N. J. C. King, et al. CXCR3 Signaling Reduces the Severity of Experimental Autoimmune Encephalomyelitis by Controlling the Parenchymal Distribution of Effector and Regulatory T Cells in the Central Nervous System J. Immunol., September 1, 2007; 179(5): 2774 - 2786. [Abstract] [Full Text] [PDF]
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I. Kryczek, S. Wei, L. Vatan, J. Escara-Wilke, W. Szeliga, E. T. Keller, and W. Zou Cutting Edge: Opposite Effects of IL-1 and IL-2 on the Regulation of IL-17+ T Cell Pool IL-1 Subverts IL-2-Mediated Suppression J. Immunol., August 1, 2007; 179(3): 1423 - 1426. [Abstract] [Full Text] [PDF]
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