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

约一半的日本人口感染幽门螺杆菌（H.pylori），除非根除，否则不可避免地导致慢性胃炎。由于慢性萎缩性胃炎患者易患胃癌，胃癌是日本的主要杀手疾病，因此研究幽门螺杆菌胃炎的发病机制非常重要。日本许多关于幽门螺杆菌胃炎的临床研究表明，感染菌株的毒力因子不能预测感染宿主胃炎的预后和多样性，由于宿主的免疫和炎症反应参与了感染胃的组织再生和上皮细胞的分化，并且炎症反应的长期效应可能在癌变中起作用，我们建立了幽门螺杆菌胃炎模型，并研究了宿主免疫反应如何调节局部炎症反应并决定胃上皮的组织再生和细胞更新。沿着的还有幽门螺杆菌感染者胃内局部免疫反应的分析，以及免疫反应类型与疾病临床表现的相关性。我们发现，在感染的胃中，由CD4T细胞产生的Th1型细胞因子在胃上皮的组织损伤和组织再生中起重要作用。此外，我们还发现胃中的Th应答与幽门螺杆菌感染的临床表现相关，即慢性胃炎和十二指肠溃疡，它们分别与胃癌的低风险和高风险相关。我们的研究结果可能有助于发现新的生物标志物，帮助识别胃癌高危患者。

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.