Open AccessJournal Article
Interleukin-13: Central mediator of allergic asthma
Marsha Wills-Karp,Jackie Luyimbazi,Xueying Xu,Brian Schofield,Tamlyn Neben,Christopher L. Karp,Debra D. Donaldson +6 more
TLDR
In this article, 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.Abstract:
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.read more
Citations
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Journal ArticleDOI
Structural Basis of Signaling Blockade by Anti-IL-13 Antibody Lebrikizumab.
Mark Ultsch,Jack Bevers,Gerald R. Nakamura,Richard Vandlen,Robert F. Kelley,Lawren C. Wu,Charles Eigenbrot +6 more
TL;DR: The molecular structure of IL-13 in complex with the Fab from lebrikizumab is reported by X-ray crystallography at 1.9Å resolution and it is shown that lebrikszumab inhibits IL- 13 signaling by binding to IL-14 with very high affinity and blocking IL-3Rα binding toIL-4Rα.
Journal ArticleDOI
IL-13Rα2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice
Mark S. Wilson,Eldad Elnekave,Margaret M. Mentink-Kane,Marcus G. Hodges,John T. Pesce,Thirumalai R. Ramalingam,Robert W. Thompson,Masahito Kamanaka,Richard A. Flavell,Andrea Keane-Myers,Allen W. Cheever,Thomas A. Wynn +11 more
TL;DR: It is demonstrated that increased IL-13 receptor alpha 2 (IL-13Ralpha2) expression is responsible for the reduced AHR, mucus production, and fibrosis in BALB/c IL-10(-/-) mice.
Journal ArticleDOI
Interleukin (IL)-4 and IL-13 up-regulate monocyte chemoattractant protein-1 expression in human bronchial epithelial cells: involvement of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2 and Janus kinase-2 but not c-Jun NH2-terminal kinase 1/2 signalling pathways.
TL;DR: IL‐4 and IL‐13 were found to up‐regulate gene expression and significantly increase the release of MCP‐1 from BEAS‐2B cells, illustrating that the activation of p38 MAPK, ERK and JAK‐2 but not JNK is crucial for IL‐4‐ andIL‐13‐induced MCP•1 release in human bronchial epithelial cells.
Journal ArticleDOI
Airway remodeling in asthma: therapeutic implications of mechanisms.
Robert J. Homer,Jack A. Elias +1 more
TL;DR: Transgenic modeling of inflammatory mediators allows for the discovery of unexpected effects, dissection of downstream signaling events, and clues to future therapies in asthma.
Journal ArticleDOI
Neonatal Chlamydial Infection Induces Mixed T-Cell Responses That Drive Allergic Airway Disease
Jay C. Horvat,Kenneth W. Beagley,Margaret A. Wade,Julie A. Preston,Nicole G. Hansbro,Danica K. Hickey,Gerard E. Kaiko,Peter G. Gibson,Paul S. Foster,Philip M. Hansbro +9 more
TL;DR: Early-life chlamydial infection induces a mixed type 1 and 2 T-cell response to antigen, which differentially affects the development of key features of AAD in the adult.
References
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Journal ArticleDOI
Functional diversity of helper T lymphocytes.
TL;DR: The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses.
Journal ArticleDOI
Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma
Douglas S. Robinson,Qutayba Hamid,Sun Ying,Anne Tsicopoulos,J. Barkans,Andrew Bentley,Christopher Corrigan,Stephen R. Durham,A. B. Kay +8 more
TL;DR: Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the TH2-like T-cell population.
Journal ArticleDOI
Eosinophilic inflammation in asthma.
Jean Bousquet,Pascal Chanez,J.-Y. Lacoste,G. Barneon,N Ghavanian,I. Enander,Per Venge,Staffan Ahlstedt,J Simony-Lafontaine,P. Godard +9 more
TL;DR: Eosinophilic inflammation of the airways is correlated with the severity of asthma and these cells are likely to play a part in the epithelial damage seen in this disease.
Journal ArticleDOI
Requirement for IL-13 Independently of IL-4 in Experimental Asthma
Gabriele Grünig,Martha L. Warnock,Adil E. Wakil,Rajeev Venkayya,Frank Brombacher,Donna M. Rennick,Dean Sheppard,Markus Mohrs,Debra D. Donaldson,Richard M. Locksley,David B. Corry +10 more
TL;DR: This article showed that IL-4 receptor α chain-dependent pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL4 receptor and showed that selective neutralization of IL-13, a cytokine related to interleukin-4 that also binds to the α chain of the IL 4 receptor, ameliorated asthma phenotype.
Journal ArticleDOI
Cellular events in the bronchi in mild asthma and after bronchial provocation.
TL;DR: It is concluded that allergic asthma is accompanied by extensive inflammatory changes in the airways, even in mild clinical and subclinical disease.
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