Studies on host factors determining prognosis and pathophysiology of patients with Helicobacter pylori infection

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About a half of Japanese population are infected with Helicobacter pylori (H.pylori), which invariably lead to chronic gastritis unless eradicated. Since chronic atrophic form of gastritis predispose patients to develop gastric cancer, a chief killer disease in Japan, studies on pathogenesis of H.pylori gastritis is very important. Many clinical studies on H.pylori gastritis in Japan have indicated that virulence factors of infecting strains do not predict prognosis and diversity of gastritis in infected hosts.Since host immune and inflammatory reactions are involved in tissue regeneration and differentiation of epithelial cells of the infected stomach and long term effects of inflammatory reactions are likely to play roles in carcinogenesis, we generated an H.pylori gastritis model and studied how host immune reactions regulate local inflammatory reaction and determine tissue regeneration and cell turnover of gastric epithelium. Along with this, we also analyzed local immune reaction in the stomach of H.pylori infected stomach and studied correlation of type of immune reactions and clinical manifestation of the disease. We found Th1 type cytokines produced by CD4T cells in the infected stomach play important roles in both tissue damage and in tissue regeneration of gastric epithelium. Moreover we found that Th responses in the stomach correlate to clinical manifestation of H.pylori infection, i.e. chronic gastritis and duodenal ulcer which are associated with low and high risk of gastric cancer, respectively. The result of our study may contribute to finding new biomarkers, which help identify high-risk patients of gastric cancers.