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CUTTING EDGE |
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* Section of Pulmonary and Critical Care Medicine,
Alcohol Research Center,
Gene Therapy Program, and
Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA 70112
Local production of IL-17 is a significant factor in effective host defense against Gram-negative bacteria. However, the proximal events mediating IL-17 elaboration by T cells remain unclear. In this study, we show in vivo that intact Toll-like receptor 4 signaling in the lung is required for induction of both the p19 transcript of IL-23 and IL-17 protein elaboration in response to Klebsiella pneumoniae. Although IL-17 is widely considered a CD4+ T cell product, we also demonstrate significant in vitro IL-17 production by CD8+ T cells after culture in medium from dendritic cells exposed to these bacteria. The dominant portion of this IL-17-inducing activity for both CD4+ and CD8+ T cells is IL-23. These data demonstrate the critical signaling pathway for IL-17 induction in the host response to Gram-negative pulmonary infection and suggest a direct role for IL-23 in CD8+ T cell IL-17 production.
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T. M. Wozniak, A. A. Ryan, and W. J. Britton Interleukin-23 Restores Immunity to Mycobacterium tuberculosis Infection in IL-12p40-Deficient Mice and Is Not Required for the Development of IL-17-Secreting T Cell Responses J. Immunol., December 15, 2006; 177(12): 8684 - 8692. [Abstract] [Full Text] [PDF]
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S. C. Higgins, A. G. Jarnicki, E. C. Lavelle, and K. H. G. Mills TLR4 Mediates Vaccine-Induced Protective Cellular Immunity to Bordetella pertussis: Role of IL-17-Producing T Cells J. Immunol., December 1, 2006; 177(11): 7980 - 7989. [Abstract] [Full Text] [PDF]
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J. R. Chan, W. Blumenschein, E. Murphy, C. Diveu, M. Wiekowski, S. Abbondanzo, L. Lucian, R. Geissler, S. Brodie, A. B. Kimball, et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis J. Exp. Med., November 27, 2006; 203(12): 2577 - 2587. [Abstract] [Full Text] [PDF]
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E. Lockhart, A. M. Green, and J. L. Flynn IL-17 Production Is Dominated by {gamma}{delta} T Cells rather than CD4 T Cells during Mycobacterium tuberculosis Infection J. Immunol., October 1, 2006; 177(7): 4662 - 4669. [Abstract] [Full Text] [PDF]
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M. Rangachari, N. Mauermann, R. R. Marty, S. Dirnhofer, M. O. Kurrer, V. Komnenovic, J. M. Penninger, and U. Eriksson T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17 J. Exp. Med., August 7, 2006; 203(8): 2009 - 2019. [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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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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F. Spensieri, G. Fedele, C. Fazio, M. Nasso, P. Stefanelli, P. Mastrantonio, and C. M. Ausiello Bordetella pertussis Inhibition of Interleukin-12 (IL-12) p70 in Human Monocyte-Derived Dendritic Cells Blocks IL-12 p35 through Adenylate Cyclase Toxin-Dependent Cyclic AMP Induction. Infect. Immun., May 1, 2006; 74(5): 2831 - 2838. [Abstract] [Full Text] [PDF]
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C. M. Tato, A. Laurence, and J. J. O'Shea Helper T cell differentiation enters a new era: Le Roi est mort; vive le Roi! J. Exp. Med., April 17, 2006; 203(4): 809 - 812. [Abstract] [Full Text] [PDF]
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G. Piskin, R. M. R. Sylva-Steenland, J. D. Bos, and M. B. M. Teunissen In Vitro and In Situ Expression of IL-23 by Keratinocytes in Healthy Skin and Psoriasis Lesions: Enhanced Expression in Psoriatic Skin J. Immunol., February 1, 2006; 176(3): 1908 - 1915. [Abstract] [Full Text] [PDF]
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M. A. Kleinschek, U. Muller, S. J. Brodie, W. Stenzel, G. Kohler, W. M. Blumenschein, R. K. Straubinger, T. McClanahan, R. A. Kastelein, and G. Alber IL-23 Enhances the Inflammatory Cell Response in Cryptococcus neoformans Infection and Induces a Cytokine Pattern Distinct from IL-12 J. Immunol., January 15, 2006; 176(2): 1098 - 1106. [Abstract] [Full Text] [PDF]
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K. I. Happel, E. A. Lockhart, C. M. Mason, E. Porretta, E. Keoshkerian, A. R. Odden, S. Nelson, and A. J. Ramsay Pulmonary Interleukin-23 Gene Delivery Increases Local T-Cell Immunity and Controls Growth of Mycobacterium tuberculosis in the Lungs Infect. Immun., September 1, 2005; 73(9): 5782 - 5788. [Abstract] [Full Text] [PDF]
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S. A. Khader, J. E. Pearl, K. Sakamoto, L. Gilmartin, G. K. Bell, D. M. Jelley-Gibbs, N. Ghilardi, F. deSauvage, and A. M. Cooper IL-23 Compensates for the Absence of IL-12p70 and Is Essential for the IL-17 Response during Tuberculosis but Is Dispensable for Protection and Antigen-Specific IFN-{gamma} Responses if IL-12p70 Is Available J. Immunol., July 15, 2005; 175(2): 788 - 795. [Abstract] [Full Text] [PDF]
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F. McAllister, A. Henry, J. L. Kreindler, P. J. Dubin, L. Ulrich, C. Steele, J. D. Finder, J. M. Pilewski, B. M. Carreno, S. J. Goldman, et al. Role of IL-17A, IL-17F, and the IL-17 Receptor in Regulating Growth-Related Oncogene-{alpha} and Granulocyte Colony-Stimulating Factor in Bronchial Epithelium: Implications for Airway Inflammation in Cystic Fibrosis J. Immunol., July 1, 2005; 175(1): 404 - 412. [Abstract] [Full Text] [PDF]
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R. Malley, K. Trzcinski, A. Srivastava, C. M. Thompson, P. W. Anderson, and M. Lipsitch CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization PNAS, March 29, 2005; 102(13): 4848 - 4853. [Abstract] [Full Text] [PDF]
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 F. Shen, M. J. Ruddy, P. Plamondon, and S. L. Gaffen Cytokines link osteoblasts and inflammation: microarray analysis of interleukin-17- and TNF-{alpha}-induced genes in bone cells J. Leukoc. Biol., March 1, 2005; 77(3): 388 - 399. [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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J. R. Schurr, E. Young, P. Byrne, C. Steele, J. E. Shellito, and J. K. Kolls Central Role of Toll-Like Receptor 4 Signaling and Host Defense in Experimental Pneumonia Caused by Gram-Negative Bacteria Infect. Immun., January 1, 2005; 73(1): 532 - 545. [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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C.-Y. Kao, Y. Chen, P. Thai, S. Wachi, F. Huang, C. Kim, R. W. Harper, and R. Wu IL-17 Markedly Up-Regulates {beta}-Defensin-2 Expression in Human Airway Epithelium via JAK and NF-{kappa}B Signaling Pathways J. Immunol., September 1, 2004; 173(5): 3482 - 3491. [Abstract] [Full Text] [PDF]
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L. A. Lieberman, F. Cardillo, A. M. Owyang, D. M. Rennick, D. J. Cua, R. A. Kastelein, and C. A. Hunter IL-23 Provides a Limited Mechanism of Resistance to Acute Toxoplasmosis in the Absence of IL-12 J. Immunol., August 1, 2004; 173(3): 1887 - 1893. [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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M. A. Olman, K. E. White, L. B. Ware, W. L. Simmons, E. N. Benveniste, S. Zhu, J. Pugin, and M. A. Matthay Pulmonary Edema Fluid from Patients with Early Lung Injury Stimulates Fibroblast Proliferation through IL-1{beta}-Induced IL-6 Expression J. Immunol., February 15, 2004; 172(4): 2668 - 2677. [Abstract] [Full Text] [PDF]
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