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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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K. M. Dhodapkar, S. Barbuto, P. Matthews, A. Kukreja, A. Mazumder, D. Vesole, S. Jagannath, and M. V. Dhodapkar Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma Blood, October 1, 2008; 112(7): 2878 - 2885. [Abstract] [Full Text] [PDF]
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Y. Laouar, T. Town, D. Jeng, E. Tran, Y. Wan, V. K. Kuchroo, and R. A. Flavell TGF-{beta} signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis PNAS, August 5, 2008; 105(31): 10865 - 10870. [Abstract] [Full Text] [PDF]
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G. H. Stummvoll, R. J. DiPaolo, E. N. Huter, T. S. Davidson, D. Glass, J. M. Ward, and E. M. Shevach Th1, Th2, and Th17 Effector T Cell-Induced Autoimmune Gastritis Differs in Pathological Pattern and in Susceptibility to Suppression by Regulatory T Cells J. Immunol., August 1, 2008; 181(3): 1908 - 1916. [Abstract] [Full Text] [PDF]
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J. Ochoa-Reparaz, A. Rynda, M. A. Ascon, X. Yang, I. Kochetkova, C. Riccardi, G. Callis, T. Trunkle, and D. W. Pascual IL-13 Production by Regulatory T Cells Protects against Experimental Autoimmune Encephalomyelitis Independently of Autoantigen J. Immunol., July 15, 2008; 181(2): 954 - 968. [Abstract] [Full Text] [PDF]
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J. H. Mills, L. F. Thompson, C. Mueller, A. T. Waickman, S. Jalkanen, J. Niemela, L. Airas, and M. S. Bynoe CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis PNAS, July 8, 2008; 105(27): 9325 - 9330. [Abstract] [Full Text] [PDF]
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P. D. Doodes, Y. Cao, K. M. Hamel, Y. Wang, B. Farkas, Y. Iwakura, and A. Finnegan Development of Proteoglycan-Induced Arthritis Is Independent of IL-17 J. Immunol., July 1, 2008; 181(1): 329 - 337. [Abstract] [Full Text] [PDF]
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T. Khayrullina, J.-H. Yen, H. Jing, and D. Ganea In Vitro Differentiation of Dendritic Cells in the Presence of Prostaglandin E2 Alters the IL-12/IL-23 Balance and Promotes Differentiation of Th17 Cells J. Immunol., July 1, 2008; 181(1): 721 - 735. [Abstract] [Full Text] [PDF]
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S. Serada, M. Fujimoto, M. Mihara, N. Koike, Y. Ohsugi, S. Nomura, H. Yoshida, T. Nishikawa, F. Terabe, T. Ohkawara, et al. IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis PNAS, July 1, 2008; 105(26): 9041 - 9046. [Abstract] [Full Text] [PDF]
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J. R. Lees, Y. Iwakura, and J. H. Russell Host T Cells Are the Main Producers of IL-17 within the Central Nervous System during Initiation of Experimental Autoimmune Encephalomyelitis Induced by Adoptive Transfer of Th1 Cell Lines J. Immunol., June 15, 2008; 180(12): 8066 - 8072. [Abstract] [Full Text] [PDF]
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M.-L. Chen, B.-S. Yan, Y. Bando, V. K. Kuchroo, and H. L. Weiner Latency-Associated Peptide Identifies a Novel CD4+CD25+ Regulatory T Cell Subset with TGF{beta}-Mediated Function and Enhanced Suppression of Experimental Autoimmune Encephalomyelitis J. Immunol., June 1, 2008; 180(11): 7327 - 7337. [Abstract] [Full Text] [PDF]
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R.-N. E. Dogan, A. Elhofy, and W. J. Karpus Production of CCL2 by Central Nervous System Cells Regulates Development of Murine Experimental Autoimmune Encephalomyelitis through the Recruitment of TNF- and iNOS-Expressing Macrophages and Myeloid Dendritic Cells J. Immunol., June 1, 2008; 180(11): 7376 - 7384. [Abstract] [Full Text] [PDF]
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 N. Yusuf, T. H. Nasti, S. K. Katiyar, M. K. Jacobs, M. D. Seibert, A. C. Ginsburg, L. Timares, H. Xu, and C. A. Elmets Antagonistic Roles of CD4+ and CD8+ T-Cells in 7,12-Dimethylbenz(a)anthracene Cutaneous Carcinogenesis Cancer Res., May 15, 2008; 68(10): 3924 - 3930. [Abstract] [Full Text] [PDF]
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J. Liu, F. Lin, M. G. Strainic, F. An, R. H. Miller, C. Z. Altuntas, P. S. Heeger, V. K. Tuohy, and M. E. Medof IFN-{gamma} and IL-17 Production in Experimental Autoimmune Encephalomyelitis Depends on Local APC-T Cell Complement Production J. Immunol., May 1, 2008; 180(9): 5882 - 5889. [Abstract] [Full Text] [PDF]
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S. Reinwald, C. Wiethe, A. M. Westendorf, M. Breloer, M. Probst-Kepper, B. Fleischer, A. Steinkasserer, J. Buer, and W. Hansen CD83 Expression in CD4+ T Cells Modulates Inflammation and Autoimmunity J. Immunol., May 1, 2008; 180(9): 5890 - 5897. [Abstract] [Full Text] [PDF]
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D. Cihakova, J. G. Barin, M. Afanasyeva, M. Kimura, D. Fairweather, M. Berg, M. V. Talor, G. C. Baldeviano, S. Frisancho, K. Gabrielson, et al. Interleukin-13 Protects Against Experimental Autoimmune Myocarditis by Regulating Macrophage Differentiation Am. J. Pathol., May 1, 2008; 172(5): 1195 - 1208. [Abstract] [Full Text] [PDF]
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T. Carlson, M. Kroenke, P. Rao, T. E. Lane, and B. Segal The Th17-ELR+ CXC chemokine pathway is essential for the development of central nervous system autoimmune disease J. Exp. Med., April 14, 2008; 205(4): 811 - 823. [Abstract] [Full Text] [PDF]
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D. Luger, P. B. Silver, J. Tang, D. Cua, Z. Chen, Y. Iwakura, E. P. Bowman, N. M. Sgambellone, C.-C. Chan, and R. R. Caspi Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category J. Exp. Med., April 14, 2008; 205(4): 799 - 810. [Abstract] [Full Text] [PDF]
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J. M. Rojo, E. Pini, G. Ojeda, R. Bello, C. Dong, R. A. Flavell, U. Dianzani, and P. Portoles CD4+ICOS+ T lymphocytes inhibit T cell activation 'in vitro' and attenuate autoimmune encephalitis 'in vivo' Int. Immunol., April 1, 2008; 20(4): 577 - 589. [Abstract] [Full Text] [PDF]
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J. J. Sabatino Jr., J. Shires, J. D. Altman, M. L. Ford, and B. D. Evavold Loss of IFN-{gamma} Enables the Expansion of Autoreactive CD4+ T Cells to Induce Experimental Autoimmune Encephalomyelitis by a Nonencephalitogenic Myelin Variant Antigen J. Immunol., April 1, 2008; 180(7): 4451 - 4457. [Abstract] [Full Text] [PDF]
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R. Winkler-Pickett, H. A. Young, J. M. Cherry, J. Diehl, J. Wine, T. Back, W. E. Bere, A. T. Mason, and J. R. Ortaldo In Vivo Regulation of Experimental Autoimmune Encephalomyelitis by NK Cells: Alteration of Primary Adaptive Responses J. Immunol., April 1, 2008; 180(7): 4495 - 4506. [Abstract] [Full Text] [PDF]
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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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