Interleukin-10 Expands Transit-Amplifying Cells While Depleting Lgr5+ Stem Cells via Inhibition of Wnt and Notch Signaling

Abstract Background & Aims: Epithelial regeneration is essential for homeostasis and mucosal barrier repair. In infectious and immune-mediated intestinal diseases, interleukin (IL)-10 is thought to enhance these processes. We aimed to define the mechanism by which IL-10 played in mucosal healing or injury. Methods: Intestinal stem cells (ISCs) cultures and mice were treated with recombinant mice IL-10 (rmIL-10). The level of cell proliferation, differentiation, death and related signaling pathways for self-renewal of ISCs were measured in vitro and in vivo.Results: It was uncovered that rmIL-10 increased the size and death, but reduced the total number of organoids. In addition, rmIL-10 depleted Lgr5+ ISCs and reduced epithelial proliferation, but enhanced the differentiation of epithelial cells and expanded numbers of transit-amplifying (TA) cells. These changes are related to the decrease of Wnt and Notch signals in vivo and in vitro. Meanwhile, increased expression of Paneth cells and decreased expression of enteroendocrine cells and goblet cells were induced by rmIL-10.Conclusions: IL-10 reduces the survival of Lgr5+ ISCs and proliferation of epithelial cells by inhibiting Notch and Wnt signaling, but promotes enhanced the differentiation of epithelial cells and expanded numbers of TA cells. Therefore, IL-10 acts as an anti-inflammatory factor, but may damage intestinal mucosa repair and maybe a potential target for the treatment of intestinal injury.