Journal
JOURNAL OF IMMUNOLOGY
Volume 173, Issue 7, Pages 4523-4528Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.173.7.4523
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Funding
- NIDDK NIH HHS [DK20593, T32DK07563] Funding Source: Medline
- NIGMS NIH HHS [GM42550] Funding Source: Medline
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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 (150 vs V50, respectively) can signal increased Stat6-dependent transcriptional activity, whether in an 150, Q551 or 150, 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.
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