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*
Deutsches Rheumaforschungszentrum, Berlin, Germany;
Genetics Institute, Cambridge, MA 02140; and
Medizinische Klinik m.S. Rheumatologie/Klinische Immunologie, Universitätsklinikum Charité, Berlin, Germany
Naive Th cells can be directed in vitro to develop into Th1 or Th2
cells by IL-12 or IL-4, respectively. In vivo, chronic immune reactions
lead to polarized Th cytokine patterns. We found earlier that
Borrelia burgdorferi, the spirochaete that causes Lyme
disease, induces Th1 development in 
TCR-transgenic Th cells.
Here, we used TCR-transgenic Th cells and oligonucleotide arrays to
analyze the differences between Th1 cells induced by IL-12 vs those
induced by B. burgdorferi. Transgenic Th cells primed
with peptide in the presence of B. burgdorferi expressed
several mRNAs, including the mRNA encoding IL-17, at significantly
higher levels than Th cells primed with peptide and IL-12. Cytometric
single-cell analysis of Th cell cytokine production revealed that IL-17
cannot be categorized as either Th1 or Th2 cytokine. Instead, almost
all IL-17-producing Th cells simultaneously produced TNF- and most
IL-17+ Th cells also produced GM-CSF. This pattern was also
observed in humans. Th cells from synovial fluid of patients with Lyme
arthritis coexpressed IL-17 and TNF- upon polyclonal stimulation.
The induction of IL-17 production in Th cells is not restricted to
B. burgdorferi. Priming of TCR-transgenic Th cells in
the presence of mycobacterial lysates also induced IL-17/TNF-
coproduction. The physiological stimulus for IL-17 production was
hitherto unknown. We show here for the first time that microbial
stimuli induce the expression of IL-17 together with TNF- in both
murine and human T cells. Chronic IL-17 expression induced by microbes
could be an important mediator of infection-induced
immunopathology.
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 J. J. Yu, M. J. Ruddy, H. R. Conti, K. Boonanantanasarn, and S. L. Gaffen The Interleukin-17 Receptor Plays a Gender-Dependent Role in Host Protection against Porphyromonas gingivalis-Induced Periodontal Bone Loss Infect. Immun., September 1, 2008; 76(9): 4206 - 4213. [Abstract] [Full Text] [PDF]
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 N. J. Kotloski, D. T. Nardelli, S. H. Peterson, J. R. Torrealba, T. F. Warner, S. M. Callister, and R. F. Schell Interleukin-23 Is Required for Development of Arthritis in Mice Vaccinated and Challenged with Borrelia Species Clin. Vaccine Immunol., August 1, 2008; 15(8): 1199 - 1207. [Abstract] [Full Text] [PDF]
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H. Liu and C. Rohowsky-Kochan Regulation of IL-17 in Human CCR6+ Effector Memory T Cells J. Immunol., June 15, 2008; 180(12): 7948 - 7957. [Abstract] [Full Text] [PDF]
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 V. Paunovic, H. P. Carroll, K. Vandenbroeck, and M. Gadina Signalling, inflammation and arthritis: Crossed signals: the role of interleukin (IL)-12, -17, -23 and -27 in autoimmunity Rheumatology, June 1, 2008; 47(6): 771 - 776. [Abstract] [Full Text] [PDF]
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K. Tanaka, K. Ichiyama, M. Hashimoto, H. Yoshida, T. Takimoto, G. Takaesu, T. Torisu, T. Hanada, H. Yasukawa, S. Fukuyama, et al. Loss of Suppressor of Cytokine Signaling 1 in Helper T Cells Leads to Defective Th17 Differentiation by Enhancing Antagonistic Effects of IFN-{gamma} on STAT3 and Smads J. Immunol., March 15, 2008; 180(6): 3746 - 3756. [Abstract] [Full Text] [PDF]
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K. S. Weber, M. J. Miller, and P. M. Allen Th17 Cells Exhibit a Distinct Calcium Profile from Th1 and Th2 Cells and Have Th1-Like Motility and NF-AT Nuclear Localization J. Immunol., February 1, 2008; 180(3): 1442 - 1450. [Abstract] [Full Text] [PDF]
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D. T. Nardelli, S. M. Callister, and R. F. Schell Lyme Arthritis: Current Concepts and a Change in Paradigm Clin. Vaccine Immunol., January 1, 2008; 15(1): 21 - 34. [Full Text] [PDF]
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J. H. Niess, F. Leithauser, G. Adler, and J. Reimann Commensal Gut Flora Drives the Expansion of Proinflammatory CD4 T Cells in the Colonic Lamina Propria under Normal and Inflammatory Conditions J. Immunol., January 1, 2008; 180(1): 559 - 568. [Abstract] [Full Text] [PDF]
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 D. Montufar-Solis, J. Schaefer, M. J. Hicks, and J. R. Klein Massive but selective cytokine dysregulation in the colon of IL-10 / mice revealed by multiplex analysis Int. Immunol., January 1, 2008; 20(1): 141 - 154. [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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C. L. Roark, J. D. French, M. A. Taylor, A. M. Bendele, W. K. Born, and R. L. O'Brien Exacerbation of Collagen-Induced Arthritis by Oligoclonal, IL-17-Producing {gamma}{delta} T Cells J. Immunol., October 15, 2007; 179(8): 5576 - 5583. [Abstract] [Full Text] [PDF]
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 A. Linden A Role for the Cytoplasmic Adaptor Protein Act1 in Mediating IL-17 Signaling Sci. Signal., August 7, 2007; 2007(398): re4 - re4. [Abstract] [Full Text] [PDF]
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F. Annunziato, L. Cosmi, V. Santarlasci, L. Maggi, F. Liotta, B. Mazzinghi, E. Parente, L. Fili, S. Ferri, F. Frosali, et al. Phenotypic and functional features of human Th17 cells J. Exp. Med., August 6, 2007; 204(8): 1849 - 1861. [Abstract] [Full Text] [PDF]
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S. Nakae, Y. Iwakura, H. Suto, and S. J. Galli Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17 J. Leukoc. Biol., May 1, 2007; 81(5): 1258 - 1268. [Abstract] [Full Text] [PDF]
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S. Nakae, H. Suto, G. J. Berry, and S. J. Galli Mast cell-derived TNF can promote Th17 cell-dependent neutrophil recruitment in ovalbumin-challenged OTII mice Blood, May 1, 2007; 109(9): 3640 - 3648. [Abstract] [Full Text] [PDF]
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M. Umemura, A. Yahagi, S. Hamada, M. D. Begum, H. Watanabe, K. Kawakami, T. Suda, K. Sudo, S. Nakae, Y. Iwakura, et al. IL-17-Mediated Regulation of Innate and Acquired Immune Response against Pulmonary Mycobacterium bovis Bacille Calmette-Guerin Infection J. Immunol., March 15, 2007; 178(6): 3786 - 3796. [Abstract] [Full Text] [PDF]
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H. H. Hofstetter, K. V. Toyka, M. Tary-Lehmann, and P. V. Lehmann Kinetics and Organ Distribution of IL-17-Producing CD4 Cells in Proteolipid Protein 139-151 Peptide-Induced Experimental Autoimmune Encephalomyelitis of SJL Mice J. Immunol., February 1, 2007; 178(3): 1372 - 1378. [Abstract] [Full Text] [PDF]
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R. C. Axtell, L. Xu, S. R. Barnum, and C. Raman CD5-CK2 Binding/Activation-Deficient Mice Are Resistant to Experimental Autoimmune Encephalomyelitis: Protection Is Associated with Diminished Populations of IL-17-Expressing T Cells in the Central Nervous System J. Immunol., December 15, 2006; 177(12): 8542 - 8549. [Abstract] [Full Text] [PDF]
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V. A. Dennis, A. Jefferson, S. R. Singh, F. Ganapamo, and M. T. Philipp Interleukin-10 Anti-Inflammatory Response to Borrelia burgdorferi, the Agent of Lyme Disease: a Possible Role for Suppressors of Cytokine Signaling 1 and 3. Infect. Immun., October 1, 2006; 74(10): 5780 - 5789. [Abstract] [Full Text] [PDF]
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C. Keller, R. Hoffmann, R. Lang, S. Brandau, C. Hermann, and S. Ehlers Genetically Determined Susceptibility to Tuberculosis in Mice Causally Involves Accelerated and Enhanced Recruitment of Granulocytes Infect. Immun., July 1, 2006; 74(7): 4295 - 4309. [Abstract] [Full Text] [PDF]
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Y. Komiyama, S. Nakae, T. Matsuki, A. Nambu, H. Ishigame, S. Kakuta, K. Sudo, and Y. Iwakura IL-17 Plays an Important Role in the Development of Experimental Autoimmune Encephalomyelitis J. Immunol., July 1, 2006; 177(1): 566 - 573. [Abstract] [Full Text] [PDF]
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 S. Lajoie-Kadoch, P. Joubert, S. Letuve, A. J. Halayko, J. G. Martin, A. Soussi-Gounni, and Q. Hamid TNF-{alpha} and IFN-{gamma} inversely modulate expression of the IL-17E receptor in airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1238 - L1246. [Abstract] [Full Text] [PDF]
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W. Tan, W. Huang, Q. Zhong, and P. Schwarzenberger IL-17 Receptor Knockout Mice Have Enhanced Myelotoxicity and Impaired Hemopoietic Recovery Following Gamma Irradiation J. Immunol., May 15, 2006; 176(10): 6186 - 6193. [Abstract] [Full Text] [PDF]
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 J. Li, E. Simeoni, S. Fleury, J. Dudler, E. Fiorini, L. Kappenberger, L. K. von Segesser, and G. Vassalli Gene transfer of soluble interleukin-17 receptor prolongs cardiac allograft survival in a rat model. Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 779 - 783. [Abstract] [Full Text] [PDF]
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M. Numasaki, M. Watanabe, T. Suzuki, H. Takahashi, A. Nakamura, F. McAllister, T. Hishinuma, J. Goto, M. T. Lotze, J. K. Kolls, et al. IL-17 Enhances the Net Angiogenic Activity and In Vivo Growth of Human Non-Small Cell Lung Cancer in SCID Mice through Promoting CXCR-2-Dependent Angiogenesis J. Immunol., November 1, 2005; 175(9): 6177 - 6189. [Abstract] [Full Text] [PDF]
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E. Lubberts, P. Schwarzenberger, W. Huang, J. R. Schurr, J. J. Peschon, W. B. van den Berg, and J. K. Kolls Requirement of IL-17 Receptor Signaling in Radiation-Resistant Cells in the Joint for Full Progression of Destructive Synovitis J. Immunol., September 1, 2005; 175(5): 3360 - 3368. [Abstract] [Full Text] [PDF]
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 S. Nakae, H. Suto, M. Kakurai, J. D. Sedgwick, M. Tsai, and S. J. Galli Mast cells enhance T cell activation: Importance of mast cell-derived TNF PNAS, May 3, 2005; 102(18): 6467 - 6472. [Abstract] [Full Text] [PDF]
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C. L. Langrish, Y. Chen, W. M. Blumenschein, J. Mattson, B. Basham, J. D. Sedgwick, T. McClanahan, R. A. Kastelein, and D. J. Cua IL-23 drives a pathogenic T cell population that induces autoimmune inflammation J. Exp. Med., January 18, 2005; 201(2): 233 - 240. [Abstract] [Full Text] [PDF]
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 A. Linden, M. Laan, and G. P. Anderson Neutrophils, interleukin-17A and lung disease Eur. Respir. J., January 1, 2005; 25(1): 159 - 172. [Abstract] [Full Text] [PDF]
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 X. K. Liu, X. Lin, and S. L. Gaffen Crucial Role for Nuclear Factor of Activated T Cells in T Cell Receptor-mediated Regulation of Human Interleukin-17 J. Biol. Chem., December 10, 2004; 279(50): 52762 - 52771. [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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S. Nakae, A. Nambu, K. Sudo, and Y. Iwakura Suppression of Immune Induction of Collagen-Induced Arthritis in IL-17-Deficient Mice J. Immunol., December 1, 2003; 171(11): 6173 - 6177. [Abstract] [Full Text] [PDF]
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C. R. Brown, V. A. Blaho, and C. M. Loiacono Susceptibility to Experimental Lyme Arthritis Correlates with KC and Monocyte Chemoattractant Protein-1 Production in Joints and Requires Neutrophil Recruitment Via CXCR2 J. Immunol., July 15, 2003; 171(2): 893 - 901. [Abstract] [Full Text] [PDF]
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M. A. Burchill, D. T. Nardelli, D. M. England, D. J. DeCoster, J. A. Christopherson, S. M. Callister, and R. F. Schell Inhibition of Interleukin-17 Prevents the Development of Arthritis in Vaccinated Mice Challenged with Borrelia burgdorferi Infect. Immun., June 1, 2003; 71(6): 3437 - 3442. [Abstract] [Full Text] [PDF]
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K. I. Happel, M. Zheng, E. Young, L. J. Quinton, E. Lockhart, A. J. Ramsay, J. E. Shellito, J. R. Schurr, G. J. Bagby, S. Nelson, et al. Cutting Edge: Roles of Toll-Like Receptor 4 and IL-23 in IL-17 Expression in Response to Klebsiella pneumoniae Infection J. Immunol., May 1, 2003; 170(9): 4432 - 4436. [Abstract] [Full Text] [PDF]
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D. R. Chung, D. L. Kasper, R. J. Panzo, T. Chtinis, M. J. Grusby, M. H. Sayegh, and A. O. Tzianabos CD4+ T Cells Mediate Abscess Formation in Intra-abdominal Sepsis by an IL-17-Dependent Mechanism J. Immunol., February 15, 2003; 170(4): 1958 - 1963. [Abstract] [Full Text] [PDF]
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S. Ferretti, O. Bonneau, G. R. Dubois, C. E. Jones, and A. Trifilieff IL-17, Produced by Lymphocytes and Neutrophils, Is Necessary for Lipopolysaccharide-Induced Airway Neutrophilia: IL-15 as a Possible Trigger J. Immunol., February 15, 2003; 170(4): 2106 - 2112. [Abstract] [Full Text] [PDF]
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S. Nakae, Y. Komiyama, S. Narumi, K. Sudo, R. Horai, Y.-i. Tagawa, K. Sekikawa, K. Matsushima, M. Asano, and Y. Iwakura IL-1-induced tumor necrosis factor-{alpha} elicits inflammatory cell infiltration in the skin by inducing IFN-{gamma}-inducible protein 10 in the elicitation phase of the contact hypersensitivity response Int. Immunol., February 1, 2003; 15(2): 251 - 260. [Abstract] [Full Text] [PDF]
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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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 P. W. Hellings, A. Kasran, Z. Liu, P. Vandekerckhove, A. Wuyts, L. Overbergh, C. Mathieu, and J. L. Ceuppens Interleukin-17 Orchestrates the Granulocyte Influx into Airways after Allergen Inhalation in a Mouse Model of Allergic Asthma Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 42 - 50. [Abstract] [Full Text] [PDF]
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D. R. Chung, T. Chitnis, R. J. Panzo, D. L. Kasper, M. H. Sayegh, and A. O. Tzianabos CD4+ T Cells Regulate Surgical and Postinfectious Adhesion Formation J. Exp. Med., June 3, 2002; 195(11): 1471 - 1478. [Abstract] [Full Text] [PDF]
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S. Aggarwal and A. L. Gurney IL-17: prototype member of an emerging cytokine family J. Leukoc. Biol., January 1, 2002; 71(1): 1 - 8. [Abstract] [Full Text] [PDF]
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G. Pan, D. French, W. Mao, M. Maruoka, P. Risser, J. Lee, J. Foster, S. Aggarwal, K. Nicholes, S. Guillet, et al. Forced Expression of Murine IL-17E Induces Growth Retardation, Jaundice, a Th2-Biased Response, and Multiorgan Inflammation in Mice J. Immunol., December 1, 2001; 167(11): 6559 - 6567. [Abstract] [Full Text] [PDF]
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 J. Panelius, P. Lahdenne, H. Saxen, T. Heikkila, and I. Seppala Recombinant Flagellin A Proteins from Borrelia burgdorferi Sensu Stricto, B. afzelii, and B. garinii in Serodiagnosis of Lyme Borreliosis J. Clin. Microbiol., November 1, 2001; 39(11): 4013 - 4019. [Abstract] [Full Text] [PDF]
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P. Ye, P. B. Garvey, P. Zhang, S. Nelson, G. Bagby, W. R. Summer, P. Schwarzenberger, J. E. Shellito, and J. K. Kolls Interleukin-17 and Lung Host Defense against Klebsiella pneumoniae Infection Am. J. Respir. Cell Mol. Biol., September 1, 2001; 25(3): 335 - 340. [Abstract] [Full Text] [PDF]
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P. Ye, F. H. Rodriguez, S. Kanaly, K. L. Stocking, J. Schurr, P. Schwarzenberger, P. Oliver, W. Huang, P. Zhang, J. Zhang, et al. Requirement of Interleukin 17 Receptor Signaling for Lung CXC Chemokine and Granulocyte Colony-stimulating Factor Expression, Neutrophil Recruitment, and Host Defense J. Exp. Med., August 20, 2001; 194(4): 519 - 528. [Abstract] [Full Text] [PDF]
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 T. Kamradt and N. A. Mitchison Tolerance and Autoimmunity N. Engl. J. Med., March 1, 2001; 344(9): 655 - 664. [Full Text] [PDF]
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
