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Science 18 December 1998:
Vol. 282. no. 5397, pp. 2261 - 2263
DOI: 10.1126/science.282.5397.2261
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Reports

Requirement for IL-13 Independently of IL-4 in Experimental Asthma

Gabriele Grünig, Martha Warnock, Adil E. Wakil, Rajeev Venkayya, Frank Brombacher, Donna M. Rennick, Dean Sheppard, Markus Mohrs, Debra D. Donaldson, Richard M. Locksley, David B. Corry *

The pathogenesis of asthma reflects, in part, the activity of T cell cytokines. Murine models support participation of interleukin-4 (IL-4) and the IL-4 receptor in asthma. Selective neutralization of IL-13, a cytokine related to IL-4 that also binds to the alpha chain of the IL-4 receptor, ameliorated the asthma phenotype, including airway hyperresponsiveness, eosinophil recruitment, and mucus overproduction. Administration of either IL-13 or IL-4 conferred an asthma-like phenotype to nonimmunized T cell-deficient mice by an IL-4 receptor alpha  chain-dependent pathway. This pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL-4 receptor.

G. Grünig, R. Venkayya, D. Sheppard, D. B. Corry, Departments of Medicine and the Lung Biology Center at the San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94143, USA. M. Warnock, Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA. A. E. Wakil, Department of Transplantation, California Pacific Medical Center, San Francisco, CA 94115, USA. F. Brombacher, Department of Immunology at the Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa. D. M. Rennick, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA. M. Mohrs, Department of Microbiology/Immunology and the Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA. D. D. Donaldson, Genetics Institute, Cambridge, MA 02140, USA. R. M. Locksley, Departments of Medicine and Microbiology/Immunology, and the Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA.
*   To whom correspondence should be addressed. E-mail: habari{at}itsa.ucsf.edu

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Clin. Cancer Res. 13, 3125-3132
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Ethnicity-specific Gene-Gene Interaction between IL-13 and IL-4R{alpha} among African Americans with Asthma.
N. C. Battle, S. Choudhry, H.-J. Tsai, C. Eng, G. Kumar, K. B. Beckman, M. Naqvi, K. Meade, H. G. Watson, M. LeNoir, et al. (2007)
Am. J. Respir. Crit. Care Med. 175, 881-887
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Airway Exposure Levels of Lipopolysaccharide Determine Type 1 versus Type 2 Experimental Asthma.
Y.-K. Kim, S.-Y. Oh, S. G. Jeon, H.-W. Park, S.-Y. Lee, E.-Y. Chun, B. Bang, H.-S. Lee, M.-H. Oh, Y.-S. Kim, et al. (2007)
J. Immunol. 178, 5375-5382
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Lysophosphatidic Acid Induces Interleukin-13 (IL-13) Receptor {alpha}2 Expression and Inhibits IL-13 Signaling in Primary Human Bronchial Epithelial Cells.
Y. Zhao, D. He, J. Zhao, L. Wang, A. R. Leff, E. Wm. Spannhake, S. Georas, and V. Natarajan (2007)
J. Biol. Chem. 282, 10172-10179
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Superantigen Presentation by Airway Smooth Muscle to CD4+ T Lymphocytes Elicits Reciprocal Proasthmatic Changes in Airway Function.
H. Veler, A. Hu, S. Fatma, J. S. Grunstein, C. M. DeStephan, D. Campbell, J. S. Orange, and M. M. Grunstein (2007)
J. Immunol. 178, 3627-3636
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Efficacy of IL-13 Neutralization in a Sheep Model of Experimental Asthma.
M. T. Kasaian, D. D. Donaldson, L. Tchistiakova, K. Marquette, X.-Y. Tan, A. Ahmed, B. A. Jacobson, A. Widom, T. A. Cook, X. Xu, et al. (2007)
Am. J. Respir. Cell Mol. Biol. 36, 368-376
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IL-13 Mediates In Vivo IL-9 Activities on Lung Epithelial Cells but Not on Hematopoietic Cells.
V. Steenwinckel, J. Louahed, C. Orabona, F. Huaux, G. Warnier, A. McKenzie, D. Lison, R. Levitt, and J.-C. Renauld (2007)
J. Immunol. 178, 3244-3251
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Functional Dissection Identifies a Conserved Noncoding Sequence-1 Core That Mediates IL13 and IL4 Transcriptional Enhancement.
J. M. Strempel and D. Vercelli (2007)
J. Biol. Chem. 282, 3738-3746
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IL-13 and Epidermal Growth Factor Receptor Have Critical but Distinct Roles in Epithelial Cell Mucin Production.
G. Zhen, S. W. Park, L. T. Nguyenvu, M. W. Rodriguez, R. Barbeau, A. C. Paquet, and D. J. Erle (2007)
Am. J. Respir. Cell Mol. Biol. 36, 244-253
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Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NF{kappa}B.
H.-C. Lee and S. F. Ziegler (2007)
PNAS 104, 914-919
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The Human IL-13 Locus in Neonatal CD4+ T Cells Is Refractory to the Acquisition of a Repressive Chromatin Architecture.
R. B. Webster, Y. Rodriguez, W. T. Klimecki, and D. Vercelli (2007)
J. Biol. Chem. 282, 700-709
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IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells.
U.-A. Temann, Y. Laouar, E. E. Eynon, R. Homer, and R. A. Flavell (2007)
Int. Immunol. 19, 1-10
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Effects of a Low-Molecular-Weight CCR-3 Antagonist on Chronic Experimental Asthma.
M. Wegmann, R. Goggel, S. Sel, S. Sel, K. J. Erb, F. Kalkbrenner, H. Renz, and H. Garn (2007)
Am. J. Respir. Cell Mol. Biol. 36, 61-67
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Comparative Roles of IL-4, IL-13, and IL-4R{alpha} in Dendritic Cell Maturation and CD4+ Th2 Cell Function.
D. C. Webb, Y. Cai, K. I. Matthaei, and P. S. Foster (2007)
J. Immunol. 178, 219-227
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Antenatal risk factors, cytokines and the development of atopic disease in early childhood.
E K Chung, R L Miller, M T Wilson, S J McGeady, and J F Culhane (2007)
Arch. Dis. Child. Fetal Neonatal Ed. 92, F68-F73
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Th2 Cell-Selective Enhancement of Human IL13 Transcription by IL13-1112C>T, a Polymorphism Associated with Allergic Inflammation.
L. Cameron, R. B. Webster, J. M. Strempel, P. Kiesler, M. Kabesch, H. Ramachandran, L. Yu, D. A. Stern, P. E. Graves, I. C. Lohman, et al. (2006)
J. Immunol. 177, 8633-8642
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Allergy-Driven Alternative Splicing of IL-13 Receptor {alpha}2 Yields Distinct Membrane and Soluble Forms.
Y. Tabata, W. Chen, M. R. Warrier, A. M. Gibson, M. O. Daines, and G. K. K. Hershey (2006)
J. Immunol. 177, 7905-7912
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CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge.
A. G. P. Guedes, J. Paulin, L. Rivero-Nava, H. Kita, F. E. Lund, and M. S. Kannan (2006)
Am J Physiol Lung Cell Mol Physiol 291, L1286-L1293
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Interleukin-17 is a negative regulator of established allergic asthma.
S. Schnyder-Candrian, D. Togbe, I. Couillin, I. Mercier, F. Brombacher, V. Quesniaux, F. Fossiez, B. Ryffel, and B. Schnyder (2006)
J. Exp. Med. 203, 2715-2725
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A3 Adenosine Receptor Signaling Contributes to Airway Mucin Secretion after Allergen Challenge.
H. W. J. Young, C.-X. Sun, C. M. Evans, B. F. Dickey, and M. R. Blackburn (2006)
Am. J. Respir. Cell Mol. Biol. 35, 549-558
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N-linked glycosylation of IL-13R{alpha}2 is essential for optimal IL-13 inhibitory activity.
M. Kioi, S. Seetharam, and R. K. Puri (2006)
FASEB J 20, 2378-2380
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Inhibition of Arginase I Activity by RNA Interference Attenuates IL-13-Induced Airways Hyperresponsiveness.
M. Yang, D. Rangasamy, K. I. Matthaei, A. J. Frew, N. Zimmmermann, S. Mahalingam, D. C. Webb, D. J. Tremethick, P. J. Thompson, S. P. Hogan, et al. (2006)
J. Immunol. 177, 5595-5603
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Novel Approach to Inhibit Asthma-Mediated Lung Inflammation Using Anti-CD147 Intervention.
W. M. Gwinn, J. M. Damsker, R. Falahati, I. Okwumabua, A. Kelly-Welch, A. D. Keegan, C. Vanpouille, J. J. Lee, L. A. Dent, D. Leitenberg, et al. (2006)
J. Immunol. 177, 4870-4879
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Stat5 Expression Is Required for IgE-Mediated Mast Cell Function..
B. O. Barnstein, G. Li, Z. Wang, S. Kennedy, C. Chalfant, H. Nakajima, K. D. Bunting, and J. J. Ryan (2006)
J. Immunol. 177, 3421-3426
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The high-affinity IgE receptor (Fc{epsilon}RI): a critical regulator of airway smooth muscle cells?.
A. S. Gounni (2006)
Am J Physiol Lung Cell Mol Physiol 291, L312-L321
   Abstract »    Full Text »    PDF »


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