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Science 18 December 1998:
Vol. 282. no. 5397, pp. 2258 - 2261
DOI: 10.1126/science.282.5397.2258
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Reports

Interleukin-13: Central Mediator of Allergic Asthma

Marsha Wills-Karp, * Jackie Luyimbazi, Xueying Xu, Brian Schofield, Tamlyn Y. Neben, Christopher L. Karp, Debra D. Donaldson

The worldwide incidence, morbidity, and mortality of allergic asthma are increasing. The pathophysiological features of allergic asthma are thought to result from the aberrant expansion of CD4+ T cells producing the type 2 cytokines interleukin-4 (IL-4) and IL-5, although a necessary role for these cytokines in allergic asthma has not been demonstrable. The type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma. IL-13 induces the pathophysiological features of asthma in a manner that is independent of immunoglobulin E and eosinophils. Thus, IL-13 is critical to allergen-induced asthma but operates through mechanisms other than those that are classically implicated in allergic responses.

M. Wills-Karp, J. Luyimbazi, X. Xu, B. Schofield, Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205, USA. T. Y. Neben and D. D. Donaldson, Immunology Department, Genetics Institute, Cambridge, MA 02140, USA. C. L. Karp, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA, and Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205, USA.
*   To whom correspondence should be addressed. E-mail: mkarp{at}welchlink.welch.jhu.edu

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J. Biol. Chem. 282, 10172-10179
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Posttranscriptional Inhibition of Interferon-Gamma Production by Lead.
Y. Heo, T. K. Mondal, D. Gao, J. Kasten-Jolly, H. Kishikawa, and D. A. Lawrence (2007)
Toxicol. Sci. 96, 92-100
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
IL-2 and IL-18 Attenuation of Airway Hyperresponsiveness Requires STAT4, IFN-{gamma}, and Natural Killer Cells.
S. Matsubara, K. Takeda, T. Kodama, A. Joetham, N. Miyahara, T. Koya, C. H. Swasey, M. Okamoto, A. Dakhama, and E. W. Gelfand (2007)
Am. J. Respir. Cell Mol. Biol. 36, 324-332
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
The Chemokine Receptor D6 Has Opposing Effects on Allergic Inflammation and Airway Reactivity.
G. S. Whitehead, T. Wang, L. M. DeGraff, J. W. Card, S. A. Lira, G. J. Graham, and D. N. Cook (2007)
Am. J. Respir. Crit. Care Med. 175, 243-249
   Abstract »    Full Text »    PDF »
C5 Modulates Airway Hyperreactivity and Pulmonary Eosinophilia during Enhanced Respiratory Syncytial Virus Disease by Decreasing C3a Receptor Expression.
G. A. Melendi, S. J. Hoffman, R. A. Karron, P. M. Irusta, F. R. Laham, A. Humbles, B. Schofield, C.-H. Pan, R. Rabold, B. Thumar, et al. (2007)
J. Virol. 81, 991-999
   Abstract »    Full Text »    PDF »
Lymphopenic mice reconstituted with limited repertoire T cells develop severe, multiorgan, Th2-associated inflammatory disease.
J. D. Milner, J. M. Ward, A. Keane-Myers, and W. E. Paul (2007)
PNAS 104, 576-581
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Lung Fibrotic Responses to Particle Exposure.
J. C. Bonner (2007)
Toxicol Pathol 35, 148-153
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Critical Role of the Fc Receptor {gamma}-Chain on APCs in the Development of Allergen-Induced Airway Hyperresponsiveness and Inflammation.
K. Kitamura, K. Takeda, T. Koya, N. Miyahara, T. Kodama, A. Dakhama, T. Takai, A. Hirano, M. Tanimoto, M. Harada, et al. (2007)
J. Immunol. 178, 480-488
   Abstract »    Full Text »    PDF »
Protectin D1 Is Generated in Asthma and Dampens Airway Inflammation and Hyperresponsiveness.
B. D. Levy, P. Kohli, K. Gotlinger, O. Haworth, S. Hong, S. Kazani, E. Israel, K. J. Haley, and C. N. Serhan (2007)
J. Immunol. 178, 496-502
   Abstract »    Full Text »    PDF »
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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Eosinophils and CCR3 Regulate Interleukin-13 Transgene-Induced Pulmonary Remodeling.
P. C. Fulkerson, C. A. Fischetti, and M. E. Rothenberg (2006)
Am. J. Pathol. 169, 2117-2126
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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
   Abstract »    Full Text »    PDF »
Specific and Redundant Roles for NFAT Transcription Factors in the Expression of Mast Cell-Derived Cytokines.
M. Klein, S. Klein-Hessling, A. Palmetshofer, E. Serfling, C. Tertilt, T. Bopp, V. Heib, M. Becker, C. Taube, H. Schild, et al. (2006)
J. Immunol. 177, 6667-6674
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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
   Abstract »    Full Text »    PDF »


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