The Analyses of th Mechanism of IgE Production by Interleukin-4

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Allergic diseases are multifactorial inheritable diseases, and their genetic factor is called atopy. It is known that IL-4 and IL-13 which induce IgE production have a pivotal role in pathogenesis of allergic disease. I explored the possibility that the IL-4 receptor alpha chain (IL-4R alpha), which is shared by both LL-4R and IL-13R, is a atopy-causing gene, in this study. As a result, it turned out that 1) in atopic asthma patients, the incidence of isoleucine at 50th amino acid of JL-4R alpha was higher that that of valine, 2) the IL-4 signals were tranduced more in the isoleucine type-transfected B cell lines than the valine type, 3) the isoleucine type peripheral blood mononuclear cells generated more IgE than the valine type. These results suggest that Ile50Val substitution of IL-4R alpha could cause atopy.It is known that STAT6 is a transcription factor important for the 11-4 signals. I identified the critical portion of IL-4R alpha for STAT6 activation, and found that p47^<phox> binds to this portion. These results indicate that is P47^<phox> a new signal-transducing molecule of 11-4.It is known that there exists an alternative splicing product of IL-4, IL-4delta2. IL-4delta2 itself does not transduce the IL-4 signals, and acts as a competitive inhibitor against IL-4 on T cells. I analyzed the effects of IL-4delta2 on other kinds of cells, and found that IL-4delta2 acts as a competitive inhibitor against IL-4 on not only T cells, but also B cells and monocytes. These results create the background for the potential use of recombinant IL-4delta2 as a therapeutic reagent for allergic patients.