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*
Division of Immunology and Allergy, Department of Pediatrics, and
Department of Pathology, Stanford University, Stanford, CA 94305;
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom; and
Immunology Department, Genetics Institute, Cambridge, MA 02140
Airway hyperresponsiveness to a variety of specific and nonspecific stimuli is a cardinal feature of asthma, which affects nearly 10% of the population in industrialized countries. Eosinophilic pulmonary inflammation, eosinophil-derived products, as well as Th2 cytokines IL-13, IL-4, and IL-5, have been associated with the development of airway hyperreactivity (AHR), but the specific immunological basis underlying the development of AHR remains controversial. Herein we show that mice with targeted deletion of IL-13 failed to develop allergen-induced AHR, despite the presence of vigorous Th2-biased, eosinophilic pulmonary inflammation. However, AHR was restored in IL-13-/- mice by the administration of recombinant IL-13. Moreover, adoptive transfer of OVA-specific Th2 cells generated from TCR-transgenic IL-13-/- mice failed to induce AHR in recipient SCID mice, although such IL-13-/- Th2 cells produced high levels of IL-4 and IL-5 and induced significant airway inflammation. These studies definitively demonstrate that IL-13 is necessary and sufficient for the induction of AHR and that eosinophilic airway inflammation in the absence of IL-13 is inadequate for the induction of AHR. Therefore, treatment of human asthma with antagonists of IL-13 may be very effective.
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A. N.J. McKenzie and P. G. Fallon Decoy Receptors in the Regulation of T Helper Cell Type 2 Responses J. Exp. Med., March 17, 2003; 197(6): 675 - 679. [Full Text] [PDF]
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M. G. Chiaramonte, M. Mentink-Kane, B. A. Jacobson, A. W. Cheever, M. J. Whitters, M. E.P. Goad, A. Wong, M. Collins, D. D. Donaldson, M. J. Grusby, et al. Regulation and Function of the Interleukin 13 Receptor {alpha} 2 During a T Helper Cell Type 2-dominant Immune Response J. Exp. Med., March 17, 2003; 197(6): 687 - 701. [Abstract] [Full Text] [PDF]
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C. A. Herrick, L. Xu, A. N. J. McKenzie, R. E. Tigelaar, and K. Bottomly IL-13 Is Necessary, Not Simply Sufficient, for Epicutaneously Induced Th2 Responses to Soluble Protein Antigen J. Immunol., March 1, 2003; 170(5): 2488 - 2495. [Abstract] [Full Text] [PDF]
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C. Schramm, U. Herz, J. Podlech, M. Protschka, S. Finotto, M. J. Reddehase, H. Kohler, P. R. Galle, A. W. Lohse, and M. Blessing TGF-{beta} Regulates Airway Responses Via T Cells J. Immunol., February 1, 2003; 170(3): 1313 - 1319. [Abstract] [Full Text] [PDF]
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W. M. Abraham Of Mice and Men Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 1 - 4. [Full Text] [PDF]
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C. Taube, C. Duez, Z.-H. Cui, K. Takeda, Y.-H. Rha, J.-W. Park, A. Balhorn, D. D. Donaldson, A. Dakhama, and E. W. Gelfand The Role of IL-13 in Established Allergic Airway Disease J. Immunol., December 1, 2002; 169(11): 6482 - 6489. [Abstract] [Full Text] [PDF]
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F. Kheradmand, A. Kiss, J. Xu, S.-H. Lee, P. E. Kolattukudy, and D. B. Corry A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease J. Immunol., November 15, 2002; 169(10): 5904 - 5911. [Abstract] [Full Text] [PDF]
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L. Whittaker, N. Niu, U.-A. Temann, A. Stoddard, R. A. Flavell, A. Ray, R. J. Homer, and L. Cohn Interleukin-13 Mediates a Fundamental Pathway for Airway Epithelial Mucus Induced by CD4 T Cells and Interleukin-9 Am. J. Respir. Cell Mol. Biol., November 1, 2002; 27(5): 593 - 602. [Abstract] [Full Text] [PDF]
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A. M. Khan, O. Elidemir, C. E. Epstein, K. P. Lally, H. Xue, M. Blackburn, G. L. Larsen, and G. N. Colasurdo Meconium aspiration produces airway hyperresponsiveness and eosinophilic inflammation in a murine model Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L785 - L790. [Abstract] [Full Text] [PDF]
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M. E. H. Bashir, P. Andersen, I. J. Fuss, H. N. Shi, and C. Nagler-Anderson An Enteric Helminth Infection Protects Against an Allergic Response to Dietary Antigen J. Immunol., September 15, 2002; 169(6): 3284 - 3292. [Abstract] [Full Text] [PDF]
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T. Kohyama, T. A. Wyatt, X. Liu, F.-Q. Wen, T. Kobayashi, Q. Fang, H. J. Kim, and S. I. Rennard PGD2 Modulates Fibroblast-Mediated Native Collagen Gel Contraction Am. J. Respir. Cell Mol. Biol., September 1, 2002; 27(3): 375 - 381. [Abstract] [Full Text] [PDF]
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Y. Shibata, T. Kamata, M. Kimura, M. Yamashita, C.-R. Wang, K. Murata, M. Miyazaki, M. Taniguchi, N. Watanabe, and T. Nakayama Ras Activation in T Cells Determines the Development of Antigen-Induced Airway Hyperresponsiveness and Eosinophilic Inflammation J. Immunol., August 15, 2002; 169(4): 2134 - 2140. [Abstract] [Full Text] [PDF]
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H. J. Kim, X. Liu, H. Wang, T. Kohyama, T. Kobayashi, F.-Q. Wen, D. J. Romberger, S. Abe, W. MacNee, I. Rahman, et al. Glutathione prevents inhibition of fibroblast-mediated collagen gel contraction by cigarette smoke Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L409 - L417. [Abstract] [Full Text] [PDF]
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