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

Helicobacter 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.
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