CD103 promotes the proinflammatory response of gastric resident CD4+ T cell in Helicobacter pylori- positive gastritis

Abstract

Abstract As an integrin found on T cell residence, CD103 is associated with the CD8+ T cell response in allogeneic transplant rejection, autoimmune diseases and cancer, but its role in infection and inflammation remains unclear. In this study, biopsy specimens of the gastric mucosa were obtained from patients with H. pylori-positive gastritis. We found that CD103 was highly expressed in CD4+T cells of the gastric mucosa from patients with H. pylori-positive gastritis. Mucosal resident CD103+CD4+T cells exhibited an increase in the CD45RO+CCR7− effector memory phenotype and high expression of the chemokines CXCR3 and CCR9 compared with those in CD103−CD4+ T cells. An In vitro coculture study demonstrated that H. pylori-specific antigen CagA/ VacA-primed dendritic cells (DCs) induced proliferation as well as IFN-γ, TNF and IL-17 production by CD103+CD4+ T cells from patients with H. pylori-positive gastritis. Furthermore, blocking CD103 with a neutralizing antibody reduced proliferation and IFN-g, TNF and IL-17 production by CD103+CD4+ T cells cocultured with DCs. Moreover, immunoprecipitation revealed that CD103 interacted with TCR α/β and CD3ζ, and activating CD103 enhanced the phosphorylation of ZAP70 induced by the TCR signal. Finally, increased T-bet and Blimp1 levels were also observed in CD103+CD4+ T cells, while activating CD103 increased T-bet and Blimp1 expression in CD4+ T cells. Our results explored the function of CD103 in gastric T cells from patients with H. pylori-positive gastritis, which may provide a therapeutic target for the treatment of gastritis