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Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma.

Authors: Tachdjian, R  Mathias, C  Al Khatib, S  Bryce, PJ  Kim, HS  Blaeser, F  O'Connor, BD  Rzymkiewicz, D  Chen, A  Holtzman, MJ  Hershey, GK  Garn, H  Harb, H  Renz, H  Oettgen, HC  Chatila, TA 
Citation: Tachdjian R, etal., J Exp Med. 2009 Sep 28;206(10):2191-204. Epub 2009 Sep 21.
Pubmed: (View Article at PubMed) PMID:19770271
DOI: Full-text: DOI:10.1084/jem.20091480

Polymorphisms in the interleukin-4 receptor alpha chain (IL-4R alpha) have been linked to asthma incidence and severity, but a causal relationship has remained uncertain. In particular, a glutamine to arginine substitution at position 576 (Q576R) of IL-4R alpha has been associated with severe asthma, especially in African Americans. We show that mice carrying the Q576R polymorphism exhibited intense allergen-induced airway inflammation and remodeling. The Q576R polymorphism did not affect proximal signal transducer and activator of transcription (STAT) 6 activation, but synergized with STAT6 in a gene target- and tissue-specific manner to mediate heightened expression of a subset of IL-4- and IL-13-responsive genes involved in allergic inflammation. Our findings indicate that the Q576R polymorphism directly promotes asthma in carrier populations by selectively augmenting IL-4R alpha-dependent signaling.


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CRRD Object Information
CRRD ID: 4890003
Created: 2010-12-13
Species: All species
Last Modified: 2010-12-13
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.