|Morimoto, Motoko - UMD,SCHL OF MED,BALTIMORE|
|Morimoto, Masahiro - FACULTY OF AG,YAMAGUCHI J|
|Zhao, Aiping - UMD,SCHL OF MED,BALTIMORE|
|Madden, Kathleen - UNIFORMED SVCS,BETHESDA M|
|Finkelman, Fred - U CINCINNATI,CINCINNATI O|
|Mentink-Kane, Margaret - NIAID,NIH,BETHESDA MD|
|Wynn, Thomas - NIAID,NIH,BETHESDA MD|
|Shea-Donohue, Terez - UMD,SCHL OF MED,BALTIMORE|
Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 15, 2005
Publication Date: January 1, 2006
Citation: Morimoto, M., Morimoto, M., Zhao, A., Madden, K., Dawson, H., Finkleman, F., Mentink-Kane, M., Urban Jr., J.F., Wynn, T., and Shea-Donohue, T. 2006. Functional importance of regional differences in localized gene expression of receptors for IL-13 in murine gut. Journal of Immunology. 176(1):491-495. Interpretive Summary: The spectrum of cytokine profiles forms the basis for host defense against infectious disease; however, cytokines can also affect non-immune function such as the physiology of the intestine that can affect the absorption of nutrients. We examined the expression of receptors for the cytokine IL-13 that is involved in protective responses to worm parasite infection and in the expression of allergic disease. The nature of host/parasite interactions, identification of the pathways and critical mediators that contribute to host resistance, the factors that modulate susceptibility to infection, and the impact of enteric parasites on intestinal function are a few of the areas of research that hold much promise for development of novel therapeutic interventions. We observed that mice that genetically lack a high affinity receptor for IL-13 that is thought to regulate the available IL-13 that interacts with intestinal tissue demonstrate a high level of inherent hyper contractility of the smooth muscle of the colon. IL-13 expression in the small intestine contributes to the reduction in the uptake of glucose and an concomitant increase in fluid in the intestinal lumen. Control of smooth muscle function in the colon may be a way to regulate the effect of IL-13 and decrease the loss of water from the body. This work will be of interest to nutritionists who study food allergy and scientists interested in the role of parasitic infection in host immunity and nutrient absorption.
Technical Abstract: IL-13 induces a STAT6-dependent hyper contractility of intestinal smooth muscle that is mediated by binding to the IL-13R'1 component of the type 2 IL-4 receptor that is linked to STAT6. IL-13 also binds to IL-13Ralpha2 that is not linked to STAT6 and functions to limit the effects of IL-13 in vivo. In this study we assessed the contribution of regional and cellular differences in the distribution of the IL-13 receptor components to the physiological regulation of smooth muscle function in WT mice and mice deficient in STAT6 or IL-13Ralpha2. Expression of IL-13 and IL-13Ralpha2 was higher in colon than in small intestine. Laser capture micro dissection of specific cell types revealed that expression of IL-13Ralpha2 was higher in smooth muscle layer when compared to levels in the epithelial cells of the mucosa. In contrast, there was a uniform distribution of IL-13alpha1 in smooth muscle, epithelia and myenteric neurons. The significant hyper contractility of smooth muscle in mice deficient in IL-13Ralpha2, but not in STAT6, shows the physiological importance of IL-13 binding to IL-13Ralpha2. The pronounced differences in the expression of IL-13Ralpha2 suggest that the gut has developed sophisticated mechanisms for controlling or targeting the physiological and pathophysiological activity of IL-13.