BMP-driven terminal differentiation of the stomach epithelium is suppressed by H. pylori via interferon signaling

Chronic inflammatory conditions of the gastrointestinal tract are often characterized by changes to epithelial homeostasis, which is controlled by signals from the stromal cells underlying the stem cell compartment. However, it is not clear how stromal-epithelial interactions are altered in the context of chronic inflammation.Here, we studied the interplay between stromal and epithelial cells in the stomach during homeostasis and during gastric infection with H. pylori, which leads to gastric gland hyperplasia and atrophy, predisposing to gastric cancer.Mechanistically, we demonstrate a critical role of IFN-y for H. pylori-driven alterations of BMP gradients. IFN-y inhibits Bmp2 expression in gastric epithelial and stromal cells, and induces stromal expression of BMP inhibitors.