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-4Ralpha) gene have been recently identified in association with different atopic disorders. To clarify the etiological relationship between the two variants, we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Va...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1999-02, Vol.162 (3), p.1227-1231
Main Authors: Mitsuyasu, H, Yanagihara, Y, Mao, X Q, Gao, P S, Arinobu, Y, Ihara, K, Takabayashi, A, Hara, T, Enomoto, T, Sasaki, S, Kawai, M, Hamasaki, N, Shirakawa, T, Hopkin, J M, Izuhara, K
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Animals
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Base Sequence
Cell Line
Genetic Variation
Humans
Hypersensitivity, Immediate - genetics
Hypersensitivity, Immediate - immunology
Immunoglobulin E - biosynthesis
Mice
Mutagenesis, Site-Directed
Oligonucleotide Probes - genetics
Promoter Regions, Genetic
Protein Conformation
Receptors, IgE - metabolism
Receptors, Interleukin-4 - chemistry
Receptors, Interleukin-4 - genetics
Receptors, Interleukin-4 - metabolism
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Signal Transduction
STAT6 Transcription Factor
Trans-Activators - metabolism
Transfection
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Summary:Two variants of the IL-4R alpha-chain (IL-4Ralpha) gene have been recently identified in association with different atopic disorders. To clarify the etiological relationship between the two variants, we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551. The substitution of Ile for Val augmented STAT6 activation, proliferation, and transcription activity of the Iepsilon promoter by IL-4, whereas that of Arg for Gln did not change these IL-4 signals. Arg551 was not associated with atopic asthma in the Japanese population. CD23 expression and IgE synthesis by IL-4 were augmented in Ile50-bearing PBMC, compared with those bearing Val50. Taken together, substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript, whereas the substitution of Ile50 contributes to enhancement of IgE synthesis.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.162.3.1227