Cutting edge: Dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis

Two variants of the IL-4R alpha-chain (IL-4R alpha) gene have been recently identified in association with different atopic disorders. To clarify the etiological relationship between the two variants, we analyzed responsivene ss to IL-4 of transfectants with four kinds of IL-4R alpha carrying either Val or ne at 50 and either Gln or Arg at 551, The substitution of Ile for V al augmented STAT6 activation, proliferation, and transcription activity of the I epsilon promoter by IL-4, whereas that of Arg for Gln did not change these IL-4 signals. Arg(551) was not associated with atopic asthma in the Japanese population. CD23 expression and IgE synthesis by IL-4 were augment ed in Ile(50)-bearing PBMC, compared with those hearing Val(50), Taken toge ther, substitution of Arg551 does not enhance the IL-4 signal for generatio n of germline epsilon transcript, whereas the substitution of Ile(50) contr ibutes to enhancement of IgE synthesis.