Tissue/Cell specific expression of IL-5 in transgenic mice induces pathophysiological changes and unique histopathologies associated with the site of expression

Several studies have shown that IL-5 is both a key mediator of eosinophil differentiation and an important agonist of effector cell activities. We have developed a series of transgenic lines of mice expressing this cytokine in a tissue and/or cell-type specific fashion. The site of expression was based on clinical studies demonstrating IL-5 expression in disease states leading to the expansion of eosinophil numbers, tissue infiltration, and the development of histopathologies. Tissue specific expression was achieved using a cDNA:Genomic fusion IL-5 gene that eliminated all known endogenous regulatory sequences. Transgenic lines were generated using promoters/enhancer regulatory elements that resulted in the expression of this gene in either mature T cells, Clara cells in the lung, or skin keratinocytes. Individuals from each line of mice uniquely developed pathophysiological changes and histopathologies spécifie to the site of IL-5 expression. In each case, the effects were accompanied by an expansion of peripheral blood eosinophil numbers, the establishment of extramedullary eosinophilopoiesis, and tissue specific infiltration. Histopathologies in some of the transgenic lines are dramatic and lead to severe complications and early death. Studies of these transgenic mice suggest that the site of IL-5 expression is an important determinant of tissue-specific eosinophil infiltration and the establishment of inflammatory responses involving eosinophils.