ArticleJournal of immunology (Baltimore, Md. : 1950)2009
An atopy-associated polymorphism in the ectodomain of the IL-4R(alpha) chain (V50) regulates the persistence of STAT6 phosphorylation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease.Pediatric rheumatology online journal · 2019Article
- IL-4Rα Polymorphism Is Associated With Myasthenia Gravis in Chinese Han Population.Frontiers in neurology · 2018Article
- IL-4 Haploinsufficiency Specifically Impairs IgE Responses against Allergens in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- An asthma-associated IL4R variant exacerbates airway inflammation by promoting conversion of regulatory T cells to TH17-like cells.Nature medicine · 2016Article
- Commentary: IL-4 and IL-13 receptors and signaling.Cytokine · 2015Article
- IL-4 receptor alpha single-nucleotide polymorphisms rs1805010 and rs1801275 are associated with increased risk of asthma in a Saudi Arabian population.Annals of thoracic medicine · 2014Article
- Impact of single nucleotide polymorphism in IL-4, IL-4R genes and systemic concentration of IL-4 on the incidence of glioma in Iraqi patients.International journal of medical sciences · 2014Article
- The M1 and M2 paradigm of macrophage activation: time for reassessment.F1000prime reports · 2014Review
- Dissociation of endotoxin tolerance and differentiation of alternatively activated macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Alternatively spliced variants of interleukin-4 promote inflammation differentially.Journal of leukocyte biology · 2011Article
- STAT6 expression in multiple cell types mediates the cooperative development of allergic airway disease.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Several commonly occurring polymorphisms in the IL-4R(alpha) have been associated with atopy in humans; the Q576R and the S503P polymorphisms reside in the cytoplasmic domain, whereas the I50 to V50 polymorphism resides in the extracellular domain of the IL-4R(alpha). The effects of these polymorphisms on signaling remain controversial. To determine the effect of the polymorphisms on IL-4 signaling in human cells, we stably transfected the human monocytic cell line U937 with murine IL-4R(alpha) cDNA bearing the I or V at position 50 and the P503/R576 double mutant. Each form of the murine IL-4R(alpha) mediated tyrosine phosphorylation of STAT6 in response to murine IL-4 treatment similar to the induction of tyrosine phosphorylation by human IL-4 signaling through the endogenous human IL-4R(alpha). After IL-4 removal, tyrosine-phosphorylated STAT6 rapidly decayed in cells expressing I50 or P503R576 murine IL-4Ralpha. In contrast, STAT6 remained significantly phosphorylated for several hours after murine IL-4 withdrawal in cells expressing the V50 polymorphism. This persistence in tyrosine-phosphorylated STAT6 was associated with persistence in CIS mRNA expression. Blocking IL-4 signaling during the decay phase using the JAK inhibitor AG490 or the anti-IL-4R(alpha) Ab M1 abrogated the persistence of phosphorylated STAT6 observed in the V50-IL-4R(alpha)-expressing cells. These results indicate that the V50 polymorphism promotes sustained STAT6 phosphorylation and that this process is mediated by continued engagement of IL-4R(alpha), suggesting enhanced responses of V50 IL-4R when IL-4 is limiting.
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