Increased infiltration of CD4+IL‐17A+FOXP3+ T cells in Helicobacter pylori‐induced gastritis

Abstract

AbstractHelicobacter pylori is one of the main predisposing factors for gastric cancer, causing chronic inflammation and proper glands atrophy in the gastric mucosa. Although H. pylori‐induced inflammation is a key inducer of precancerous lesions in the gastric mucosa, it remains unclear which precise immune cell subsets are responsible for the progression of H. pylori‐induced gastritis. Here, we observed an abundance of CD4+IL‐17A+FOXP3+ T cells exhibiting a Th17‐like phenotype within the microenvironment of H. pylori‐induced gastritis. Mechanistically, H. pylori upregulated the expression of IL‐6 in Dendritic cells and macrophages, by activating NF‐κB signaling through the virulence factor CagA and thus, induced IL‐17A expression in FOXP3+ T cells. Moreover, CD4+IL‐17A+FOXP3+ T cells were positively associated with advanced precancerous lesions. Therefore, these findings offer essential insights into how FOXP3+ T cells sense inflammatory signals from the environment, such as IL‐6, during H. pylori infections, thereby guiding the effector immune response and aggravating the gastritis.