| First Author | Tachdjian R | Year | 2009 |
| Journal | J Exp Med | Volume | 206 |
| Issue | 10 | Pages | 2191-204 |
| PubMed ID | 19770271 | Mgi Jnum | J:152376 |
| Mgi Id | MGI:4358572 | Doi | 10.1084/jem.20091480 |
| Citation | Tachdjian R, et al. (2009) Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma. J Exp Med 206(10):2191-204 |
| abstractText | 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. |
