NDLI: Distinct roles for IL-13 and IL-4 via IL-13 receptor α1 and the type II IL-4 receptor in asthma pathogenesis

Content Provider	PubMed Central
Author	Munitz, A. Brandt, E. B. Mingler, M. Finkelman, F. D. Rothenberg, M. E.
Abstract	IL-13 and IL-4 are central T helper 2 (Th2) cytokines in the immune system and potent activators of inflammatory responses and fibrosis during Th2 inflammation. Recent studies using Il13ra1 −/− mice have demonstrated a critical role for IL-13 receptor (IL-13R) α1 in allergen-induced airway responses. However, these observations require further attention especially because IL-4 can induce similar lung pathology to IL-13, independent of IL-13, and is still present in the allergic lung. Thus, we hypothesized that IL-13Rα1 regulates IL-4-induced responses in the lung. To dissect the role of IL-13Rα1 and the type I and II IL-4Rs in experimental asthma, we examined lung pathology induced by allergen, IL-4, and IL-13 challenge in Il13ra1 −/− mice. We report that IL-13Rα1 is essential for baseline IgE production, but Th2 and IgE responses to T cell-dependent antigens are IL-13Rα1-independent. Furthermore, we demonstrate that increased airway resistance, mucus, TGF-β, and eotaxin(s) production, but not cellular infiltration, are critically dependent on IL-13Rα1. Surprisingly, our results identify a CCR3- and IL-13Rα1-independent pathway for lung eosinophilia. Global expression profiling of lungs from mice stimulated with allergen or IL-4 demonstrated that marker genes of alternatively activated macrophages are differentially regulated by the type I and type II IL-4R. Taken together, our data provide a comprehensive mechanistic analysis of the critical role by which IL-13Rα1 mediates allergic lung pathology and highlight unforeseen roles for the type II IL-4R.
Related Links	http://dx.doi.org/10.1073/pnas.0802465105
Ending Page	7245
Page Count	6
Starting Page	7240
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	20
Volume Number	105
Language	English
Publisher	National Academy of Sciences
Publisher Date	2008-05-20
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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