Helicobacter pylori-induced PPFIA4 promotes gastritis and gastric bacterial colonization

Bacterial-modulated gastric epithelial cells (GECs) play key roles in H. pylori-associated pathology. Here we demonstrate both pro-colonization and pro-inflammation roles of GEC-derived PPFIA4, originally expressed in nervous system, in H. pylori infection. PPFIA4 was elevated in gastric mucosa of H. pylori-infected patients and mice. PPFIA4 in GECs was synergistically induced by H. pylori and IL-33 in a cagA-dependent manner. Human gastric PPFIA4 correlated with H. pylori colonization and the severity of gastritis, and H. pylori colonization and inflammation were attenuated in Ppfia4-/- and Ppfia4?GEC mice.Overall, we propose a model in which PPFIA4 collectively ensures H. pylori persistence and promotes gastritis. Overall design: To investigate the function of PPFIA4 in gastric epithelial cells, AGS cells were treated with PPFIA4 sgRNA or non-specific control sgRNA to generate sgPPFIA4-AGS cells and sgNC-AGS cells.