IL-17 Receptor A protects against <i>Helicobacter pylori-</i>induced gastric cancer

Abstract Infection with Helicobacter pylori is the predominant risk factor for development of gastric cancer. Risk enhanced by specific H. virulence factors, diet, and inflammatory response. Chronic activation T helper (Th) 1 Th17 pathways contribute to inflammation. Previous work suggests that while IL-17 activates several antimicrobial components innate immune response, also required prevent a hyper-inflammatory adaptive To investigate if receptor signaling contributes carcinogenesis, transgenic InsGAS mouse, which susceptible pylori-induced cancer, was used. mice Il17ra −/−mice were infected cag T4SS positive strain up 6 months. By weeks post infection, IL-17RA deficiency led increased bacterial burden gastritis, concomitant an exacerbated Th1/Th17 cytokine profile, B cell infiltration production IgA despite reduced Pigr expression. Paragastric lymph nodes −/−mice, enlarged relative mice, exhibited altered gene expression profiles potential loss fibroblastic reticular cells. Gastric pathologies, including intramucosal carcinoma adenocarcinoma submucosal invasion, developed more frequently 3 months infection in pylori-infected InsGASIl17ra −/−mice. These increases severe disease accompanied parietal cells, mucin-producing cells ceacam1. data suggest protective pathway excessive inflammation can drive carcinogenesis after infection. This supported part Merit Review I01BX000915 (Algood) from U.S. Department Veterans Affairs, Biomedical Laboratory Research Development Service. We acknowledge Translational Pathology Shared Resource NCI.NIH Cancer Center Support Grant 5P30 CA68485-19. Core Services performed through Vanderbilt University Medical Center's Digestive Disease NIH grant P30DK058404.