Dendrobium fimbriatum polysaccharide ameliorates DSS-induced intestinal mucosal injury by IL-22-regulated intestinal stem cell regeneration.

ABSTRACT

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with unknown etiology and difficult treatment. In this study, the intervention effect of Dendrobium fimbriatum Hook polysaccharide (cDFPW1) on UC was verified by constructing a dextran sulfate sodium (DSS)-induced colitis mouse model, and the protective effect of cDFPW1 on intestinal mucosal integrity in UC was explored by the co-culture system consisting of intestinal organoids and lamina propria lymphocytes (LPLs) combined with the experiment of microbial depletion mice. Results showed that cDFPW1 significantly alleviated UC symptoms in mice and promoted the proliferation of intestinal epithelial cells. Importantly, cDFPW1 could directly improve DSS-induced morphological damage of intestinal organoids and increase the number of epithelial cells, which was validated in mice. During repair, an increase in the number of Lgr5+ cells in intestinal organoids and mouse intestines was promoted by cDFPW1. Meanwhile, cDFPW1 promoted intestinal stem cells (ISCs)-mediated intestinal epithelial regeneration by significantly upregulating IL-22 expression. We further confirmed that the secretion of IL-22 was mediated by LPLs. Together, these findings suggest that cDFPW1 promotes ISCs regeneration by LPLs-mediated up-regulation of IL-22 to protect the intestinal mucosal integrity, thereby playing an important role in improving UC.