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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Prostaglandin D_2 as a Mediator of Allergic Asthma.
Matsuoka,Toshiyuki,Hirata,Masakazu,Tanaka,Hiroyuki,Takahashi,Yoshimasa,Murata,Takahiko,Kabashima,Kenji,Sugimoto,Yukihiko,Kobayashi,Takuya,Ushikubi,Fumitaka,Aze,Yoshiya,Eguchi,Naomi,Urade,Yoshihiro,Yoshida,Nobuaki,Kimura,Kazushi,Mizoguchi,Akira,Yoshihito,Nagai,Hiroichi,Narumiya,Shuh +34 more
TL;DR: PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses and is investigated by the generation of mice deficient in the PGD receptor (DP).
Journal ArticleDOI
The CD28-Related Molecule ICOS Is Required for Effective T Cell–Dependent Immune Responses
Anthony J. Coyle,Sophie M. Lehar,Clare M. Lloyd,Jane Tian,Tracy Delaney,Stephen Manning,Trang Nguyen,Tim Burwell,Helga Schneider,Jose Angel Gonzalo,Michael Gosselin,Laura Rudolph Owen,Christopher E. Rudd,Jose-Carlos Gutierrez-Ramos +13 more
TL;DR: It is suggested that ICOS, the third member of the CD28/CTLA-4 family, plays an important role in production of IL-2, IL-4, IL5, and IFNgamma from recently activated T cells and contributes to T cell-dependent B help in vivo.
Journal ArticleDOI
Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression.
Claudia L. Ordoñez,Ramin Khashayar,Hofer Wong,Ron Ferrando,Reen Wu,Dallas M. Hyde,Jon A. Hotchkiss,Yifan Zhang,Alexander Novikov,Gregory Dolganov,John V. Fahy +10 more
TL;DR: It is concluded that even mild asthma is associated with goblet cell hyperplasia and increased stored mucin in the airway epithelium, whereas moderate asthma isassociated with increased stored bronchial mucin and secreted mucin.
Journal ArticleDOI
Interleukin-4- and Interleukin-13-Mediated Alternatively Activated Macrophages: Roles in Homeostasis and Disease
TL;DR: Recent advances in the understanding of IL-4- and IL-13-mediated alternatively activated macrophages and type 2 immune responses have led to an expanded appreciation for functions of these cells beyond immunity, including maintenance of physiologic homeostasis and tissue repair.
Journal ArticleDOI
Epithelial-mesenchymal interactions in the pathogenesis of asthma.
Stephen T. Holgate,Donna E. Davies,Peter M. Lackie,Susan J. Wilson,Sarah M. Puddicombe,James L. Lordan +5 more
TL;DR: It is proposed that impaired epithelial repair cooperates with the TH2 environment to shift the set point for communication within the trophic unit and leads to myofibroblast activation, excessive matrix deposition, and production of mediators that propagate and amplify the remodeling responses throughout the airway wall.
References
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Douglas S. Robinson,Qutayba Hamid,Sun Ying,Anne Tsicopoulos,J. Barkans,Andrew Bentley,Christopher Corrigan,Stephen R. Durham,A. B. Kay +8 more
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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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