Identification and characterization of activated genes of eosinophils in asthma

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Allergic late-phase reactions provoked by specific antigens are associated with intense eosinophil infiltration into the site of antigen administration. While it is known that IL-5 plays an important role for antigen-induced eosinophil recruitment into the tissue and that IL-5 activates Stat5a and Stat5b, it is unknown about target gene (s) of IL-5 in eosinophils as well as a role of Stat5a and Stat5b in antigen-induced, IL-5-dependent eosinophil recruitment into the tissue. In this study, we addressed these points.First, to identify IL-5-inducible genes in human eosinophils, we employed Representational Difference Analysis (RDA). We found that, in addition to known targets of IL-5 signaling, such as CIS and Bcl-X, we cloned 8 novel genes from RDA clones. Five out of 8 genes were confirmed for the IL-5-induced gene expression in eosinophils by northern blotting. At present, we are trying to fish out full length cDNAs from eosinophil cDNA library. In future, we believe that the identification of target genes of IL-5 signaling in eosinophils will uncover the mechanisms of eosinophil development and the pathogenesis of allergic diseases such as asthma.Second, we analyzed the allergic properties of Stat5a-deficient (Stat5a^<-/->) and Stat5b-deficient (Stat5b^<-/->) mice. We found that antigen-induced eosinophil recruitment into the airways and IL-5 production in BALF were severely decreased in Stat5a^<-/-> mice and Stat5b^<-/-> mice. In addition, IL-5-induced eosinophilopoiesis was also impaired in Stat5a^<-/-> mice and Stat5b^<-/-> mice. These results indicate that bath Stat5a and Stat5b are essential for induction of antigen-induced eosinophil recruitment into the airways and that the defects in antigen-induced eosinophil recruitment in Stat5a^<-/-> mice and Stat5b^<-/-> mice result from both impaired IL-5 production in the airways and diminished IL-5 responsiveness of eosinophils.