MAIT cells accumulated via CXCL12-CXCR4 chemotaxis are involved in pathologic gastric inflammation among Helicobacter pylori-infected patients

BACKGROUND: Helicobacter pylori can cause gastritis, peptic ulcers, and even gastric cancer. In addition to conventional T cells, mucosal-associated invariant T (MAIT) cells may have an important immunologic role in mucosal infectious diseases. However, the phenotypic and effector characteristics of gastric MAIT cells and the relationship between mucosal MAIT cells and H. pylori-related diseases have not been established. METHODS: We analyzed the phenotypes and cytokines of gastric and peripheral MAIT cells from H. pylori-infected patients by flow cytometry. CXCL12-mediated chemotaxis of MAIT cells was measured by Transwell assay. Relationship between MAIT cells and inflammation of H. pylori-infected gastric diseases was assessed with immunofluorescence staining and histopathological score. RESULTS: The number of gastric MAIT cells was significantly increased but the frequency of peripheral MAIT cells were decreased in patients with H. pylori infections. The gastric MAIT cells were activated with high expression of CD69 and CD38, and produced several pro-inflammatory cytokines. Furthermore, we observed the expression of CXCR4 and CXCL12 were upregulated in H. pylori-infected stomachs. CXCL12 promoted MAIT cells to migrate, which was blocked by a CXCR4 antagonist. Finally, we demonstrated that the number of gastric MAIT cells was positively correlated with severe inflammation in H. pylori-infected stomachs. CONCLUSIONS: Gastric MAIT cells were accumulated and activated in H. pylori-infected stomachs, which may be involved in the pathologic inflammation of H. pylori-related gastric diseases.