Notch2 signaling is required for proper mast cell distribution and mucosal immunity in the intestine

Notch receptor-mediated signaling is involved in developmental process and functional modulation of lymphocytes, as well as mast cell differentiation. Here we investigated whether Notch signaling is required for anti-pathogen host defense regulated by mast cells. Mast cells were rarely found in the small intestine of wild-type C57BL/6 mice, while abnormally accumulated in the lamina propria of the small intestinal mucosa of the Notch2 conditional knockout mice in naive status. When transplanted into mast cell-deficient Wsh/Wsh mice, Notch2-null bone marrow-derived mast cells (BMMCs) were rarely found within the epithelial layer but abnormally localized to the lamina propria, whereas control BMMCs were mainly found within the epithelial layer. After the infection of Notch2 knockout and control mice with L3 lavae of Strongyloides venezuelensis (SV), the abundant number of mast cells was rapidly mobilized to epithelial layer in the control mice. In contrast, mast cells were massively accumulated in the lamina propria of the small intestinal mucosa in Notch2 conditional knockout mice, accompanied by impaired eradication of SV. These findings indicate that cell-autonomous Notch2 signaling in mast cells is required for proper localization of intestinal mast cells, and further imply a critical role of Notch signaling in host-pathogen interface in the small intestine.