Signal transduction via the interleukin-4 receptor and its correlation with atopy.
IL-4 and IL-13 are unique cytokines, in that they induce IgE synthesis in B cells and TH2 type differentiation in T cells. Both cytokines exert their biological activities by binding to their functional receptors on target cells. These receptors are thought to be composed as heterodimers, both having the IL-4R alpha chain (IL-4Ralpha) as a component. Among the signal-transducing molecules of IL-4 and IL-13, Stat6, which is activated by these cytokines and recruits to IL-4Ralpha, is essential for the biological activities of these cytokines. Atopy is an inherited tendency, underlying asthma, rhinitis, and eczema, and generating high non-specific IgE and/or high specific IgE against common antigens. Based on information on the molecular mechanism of the signal transduction of IL-4 and IL-13 and on some genetic studies, IL-4Ralpha was assumed to be one gene giving rise to atopy. One polymorphism existing in the IL-4Ralpha gene, Ile50Val, is verified to correlate with atopy by both genetic and functional aspects. On the contrary, the correlation between another polymorphism on the IL-4Ralpha gene, Arg551Gln, and atopy is still controversial. The strategy used in these studies should lead to identification of other genes involved in atopy.
Izuhara
K
K
Department of Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Shirakawa
T
T
D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000503:physiopathology*; D018793:Interleukin-13 / Q000235:genetics / Q000502:physiology; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4