Transcriptomics

Dataset Information

9

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


ABSTRACT: Polymorphisms in the interleukin-4 receptor α chain (IL-4Rα) 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-4Rα 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-4Rα–dependent signaling. Keywords: Cell population analysis To determine potential mechanisms underlying the trophic effects of the R576 allele on airway inflammation and remodeling, we first compared the gene expression profile in the lungs of doxycycline-treated B6.129Il4raR576/R576/IL-13tg mice versus B6.129Il4raR576/R576 littermates that lacked the IL-13tg (n = 11 and 5, respectively). We similarly compared the gene expression profile in the lungs of doxycycline-treated B6.Il4raQ576/Q576/IL-13tg mice versus tg-negative littermates (n = 8 and 5, respectively). Lastly, we directly compared the gene expression profiles in the doxycycline-treated B6.129Il4raR576/R576/IL-13tg versus B6.Il4raQ576/Q576/IL-13tg mice.

ORGANISM(S): Mus musculus  

SUBMITTER: Brian D O'Connor   Talal A Chatila  Brian O'Connor 

PROVIDER: E-GEOD-18010 | ArrayExpress | 2009-10-01

SECONDARY ACCESSION(S): GSE18010PRJNA119239

REPOSITORIES: GEO, ArrayExpress

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Publications


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 proxim  ...[more]

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