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
NF45 and NF90 regulate HS4-dependent interleukin-13 transcription in T cells.
TL;DR: HS4 acts as a position-independent, orientation-dependent positive regulator of IL13 proximal promoter activity in transiently transfected, activated human CD4+ Jurkat T cells and primary murine Th2 cells and NF45 and NF90 are identified as novel regulators of HS4-dependent human IL13 transcription in response to T cell activation.
Journal ArticleDOI
The negative-feedback regulation of the IL-13 signal by the IL-13 receptor α2 chain in bronchial epithelial cells
ichiro Yasunaga Shin,Noriko Yuyama,Kazuhiko Arima,Hiroyuki Tanaka,Shuji Toda,Miyako Maeda,Keiko Matsui,Chiho Goda,Qing Yang,Yuji Sugita,Hiroichi Nagai,Kenji Izuhara +11 more
TL;DR: The results suggested the possibility that IL-13Ralpha2 induced by its ligand is transferred to the cell surface by an unknown mechanism, and it down-regulates the IL- 13 signal in BECs, which functions as a unique negative-feedback system for the cytokine signal.
Journal ArticleDOI
The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation.
Morris Nechama,Jeahoo Kwon,Shuo Wei,Adrian Tun Kyi,Robert S. Welner,Iddo Z. Ben-Dov,Mohamed S. Arredouani,John M. Asara,Chun-Hau Chen,Cheng-Yu Tsai,Kyle F. Nelson,Koichi Kobayashi,Elliot Israel,Xiao Zhen Zhou,Linda K. Nicholson,Kun Ping Lu,Kun Ping Lu,Kun Ping Lu +17 more
TL;DR: It is shown, using biochemical, structural and patient data, that upon IL-33 or allergic challenge, the isomerase Pin1 modifies IRAK-M to control the production of pro-inflammatory cytokines in the setting of airway inflammation.
Interleukin 13 and the evolution of asthma therapy
TL;DR: The experiences with the development of neutralizing anti-IL-13 reagents emphasize the need for inclusion of a biomarker assay in the clinical trials that both identifies individuals that actually have aberrant expression of the pathway of interest and allows determining whether the target of interest is neutralized.
Journal ArticleDOI
In vivo regulation of the allergic response by the IL-4 receptor α chain immunoreceptor tyrosine-based inhibitory motif
Raffi Tachdjian,Shadi Al Khatib,Andreas Schwinglshackl,Hong Sook Kim,A. W. Chen,Julie Blasioli,Clinton B. Mathias,Hye Young Kim,Dale T. Umetsu,Hans C. Oettgen,Talal A. Chatila +10 more
TL;DR: Results point to a physiologic negative regulatory role for the Y709 ITIM in signaling through IL-4Ralpha, especially by IL-13.
References
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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.
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