Stromal Cells Induce Th17 during Helicobacter pylori Infection and in the Gastric Tumor Microenvironment

Abstract

Gastric cancer is associated with chronic inflammation and Helicobacter pylori infection. Th17 cells are CD4+ T cells associated with infections and inflammation; but their role and mechanism of induction during carcinogenesis is not understood. Gastric myofibroblasts/fibroblasts (GMF) are abundant class II MHC expressing cells that act as novel antigen presenting cells. Here we have demonstrated the accumulation of Th17 in H. pylori-infected human tissues and in the gastric tumor microenvironment. GMF isolated from human gastric cancer and H. pylori infected tissues co-cultured with CD4+ T cells induced substantially higher levels of Th17 than GMF from normal tissues in an IL-6, TGF-β, and IL-21 dependent manner. Th17 required interaction with class II MHC on GMF for activation and proliferation. These studies suggest that Th17 are induced during both H. pylori infection and gastric cancer in the inflammatory milieu of gastric stroma and may be an important link between inflammation and carcinogenesis.

Obesity acceleratesHelicobacter felis-induced gastric carcinogenesis by enhancing immature myeloid cell trafficking and TH17 response

“…1 Helicobacter pylori, a bacterium that infects humans and colonises the stomach, causing chronic gastritis and gastric cancer. [2][3][4] Among all individuals infected with H pylori, approximately 1-3% progress to gastric cancer. 1 As nearly half the world's population is infected, H pylori contributes significantly to the global gastric cancer burden.…”

Immune Responses Mediated by Th17 Cells in <b><i>Helicobacter pylori </i></b>Infection

“…Th17 required interaction with class II major histocompatibility complex on GMF for activation and proliferation. These studies suggest that Th17 cells are induced during both Hp infection and gastric cancer in the inflammatory milieu of gastric stroma and may be an important link between inflammation and carcinogenesis [29] . It should be noted that the Th17 cell immunity still lasts in the serum and mucosa even after the eradication of Hp [5] , and the persistence of IL-17A and IL-17F is considered to increase the risk of cancer [30] .…”

Role ofHelicobacter pyloriinfection in pathogenesis of gastric carcinoma

“…As reported, both cag PAI and OipA upregulate IL6 production in gastric epithelial cells [64] . Additionally, Th17 subsets are enriched in H. pylori infected muc osa [65] . The expression level of interleukin17 (IL17) has been observed to be upregulated in gastric tissues of both human and animal during H. pylori infection, while suppressed autophagy facilitates intracellular survival of this bacterium and generates an environment favoring carcinogenesis [54] .…”