| First Author | Stephenson L | Year | 2004 |
| Journal | J Immunol | Volume | 173 |
| Issue | 7 | Pages | 4523-8 |
| PubMed ID | 15383584 | Mgi Jnum | J:93726 |
| Mgi Id | MGI:3505622 | Doi | 10.4049/jimmunol.173.7.4523 |
| Citation | Stephenson L, et al. (2004) An IL-4R alpha allelic variant, I50, acts as a gain-of-function variant relative to V50 for Stat6, but not Th2 differentiation. J Immunol 173(7):4523-8 |
| abstractText | Signaling through the IL-4R alpha-chain (IL-4Ralpha) is crucial for the development of Th2 cells, central effectors in atopic disease. Alleles of the IL-4Ralpha have been identified that have been variably associated with increased incidence of allergic disease, but there is little direct evidence that any variant is sufficient to alter a target that determines allergic pathophysiology or susceptibility. Variants of IL-4Ralpha encoding isoleucine instead of valine at position 50 (I50 vs V50, respectively) can signal increased Stat6-dependent transcriptional activity, whether in an I50, Q551 or I50, R551 haplotype. Strikingly, signaling through these receptors did not increase the efficiency of Th2 development or the IL-4 mediated repression of Th1 development or a target gene, IL-18Ralpha. Further, IL-4-induced proliferation was similar for Th2 cells independent of the variant expressed. Together these findings indicate that IL-4Ralpha variants that exhibit gain-of-function with respect to Stat6 do not act directly through alterations in Th2/Th1 induction after Ag exposure. The data further suggest that for such variants, any mechanistic involvement is based on a role in cellular targets of Th2 cytokines. |
