Functional Importance of Regional Differences in Localized Gene Expression of Receptors for IL-13 in Murine Gut

Abstract

IL-13 induces a STAT6-dependent hypercontractility of intestinal smooth muscle that is mediated by binding to the IL-13Rα1 component of the type 2 IL-4R that is linked to STAT6. IL-13 also binds to the IL-13Rα2 that is not linked to STAT6 and functions to limit the effects of IL-13 in vivo. In this study we assessed the contributions of regional and cellular differences in the distribution of the IL-13R components to the physiological regulation of smooth muscle function in wild-type mice and mice deficient in STAT6 or IL-13Rα2. The expression of IL-13 and IL-13Rα2 was higher in colon than in small intestine. Laser capture microdissection of specific cell types revealed that the expression of IL-13Rα2 was higher in the smooth muscle layer compared with levels in the epithelial cells of the mucosa. In contrast, there was a uniform distribution of IL-13α1 in smooth muscle, epithelia, and myenteric neurons. The significant hypercontractility of smooth muscle in mice deficient in IL-13Rα2, but not in STAT6, shows the physiological importance of IL-13 binding to IL-13Rα2. The pronounced differences in the expression of IL-13Rα2 suggest that the gut has developed sophisticated mechanisms for controlling the physiological and pathophysiological activities of IL-13.