Identification of atopy genes and analyses of their functions

点击翻译按钮获取中文摘要

We investigated the genetic role of the IL-13 gene in the pathogenesis of allergic diseases. We found a novel single nucleotide polymorphism (SNP) which substitutes glutamine at 110 for arginine. The incidence of glutamine was higher than arginine in both atopic and non-atopic asthma patients. Serum level of IL-13 was also higher in the glutamine type. These results suggest that the IL-13 gene is an asthma-causing gene.To identify the target cells of IL-13 in lung, we generated anti-IL-13Rα1 antibody, and performed immunohistochemistry. It turned out that IL- 13Rα1 and IL-4Rα, both of which are the components of the IL-13R highly expressed on bronchial epithelial cells and bronchial smooth muscle cells. These results showed that these cells are main target cells of IL-13 in the lung tissue.We next analyzed the signal transduction mechanism of IL-13 using various types of IL- 13Rα1. Consequently, it was revealed that Tyk2 bound to the Box1 region close to its transmembrane domain, IL-13 activated STAT3 in addition to STAT6, and STAT3 bound to the tyrosine residues close to its C-terminus.