Chronic skin damage induces small intestinal damage via IL-13-induced apoptosis

Abstract

Abstract The gut–skin axis has recently been widely recognized, and both the gut and skin have been found to affect each other through a bidirectional connection; however, the precise mechanisms remain to be elucidated. Therefore, we aimed to investigate the effects of chronic skin damage (CSD) on mouse intestines. Following the CSD model, 4% sodium dodecyl sulfate was applied to the back-shaved murine skin six times for 2 weeks after tape stripping. The small and large intestines were analyzed histologically and immunologically, respectively. Intestinal permeability was measured using fluorescein isothiocyanate-conjugated-dextran. The role of interleukin-13 (IL-13) in the ileum was investigated using an anti-IL-13 antibody. Apoptotic intestinal cells were analyzed using TUNEL staining. Villus atrophy was observed in the small intestine in the CSD model, along with increased permeability. Mast cells, but not T cells, eosinophils, or innate lymph cell-2, were increased in the intestinal mucosa. However, no significant changes were observed in the large intestine. mRNA expression of IL-13 was increased only in the ileum of the CSD model. Apoptotic intestinal epithelial cells were significantly increased in the ileum of the CSD model. Administration of an anti-IL-13 antibody ameliorated the intestinal damage caused by CSD, along with decreased apoptotic cells and mast cell infiltration. Skin damage causes morphological changes in the small intestine, accompanied by increased intestinal permeability, possibly through the IL-13-induced apoptosis of mast cells in the epithelium. Surfactant-mediated mechanical skin damage can cause a leaky gut.