Mechanisms of Intestinal Epithelial Cell Regeneration from Radiation-Induced Small Intestinal Injury in Mice

Abstract

Background: Signaling by IL-4 and IL-13 is transduced via a receptor complex of IL-13Rα1 and IL-4Rα chains. However, contribution of a putative decoy receptor of IL-13, IL-13Rα2, is not clear. The aim of this study was to determine the significance of Th2-type cytokines in the gastrointestinal (GI) epithelial cell repair system. Methods: We compared the tissue recovery in wild type (WT) and IL-4 receptor α deficient (IL-4R KO) mice following mucosal damage induced by 3 Gy-whole body γ-irradiation. The expression of IL-4, IL-13 and related molecules in the regenerative process were assessed. Results: Expression of IL-13Rα2 dramatically increased in myofibroblasts and fibroblasts on day 3. In contrast, in IL-4R KO mice, intestinal tissue repair after irradiation was delayed, and the transient upregulation of IL-13Rα2 was not seen. Injection of a soluble IL-13Rα2-immunoglobulin chimeric protein to both of WT and IL-4R KO mice resulted in the improvement of tissue recovery. Addition of IL-13 into primary tissue culture of the jejunum induced epithelial cell damage with decreased expression of membrane bound β-catenin. Conclusions: Our study demonstrated that IL-13 has a potential to induce epithelial cell damage, and IL-13Rα2 functions as a regulatory factor in the regeneration of intestinal epithelial cells.