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

幽门螺杆菌感染患者预后及病理生理的宿主因素研究

• 批准号: 14370180
• 负责人: WAKATSUKI Yoshio
• 金额: $ 5.31万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370180/
• 关键词: Helicobacter pylori; pathogenicity; host factors; mucosal immunology; gastritis; gastric cancer; tissue regeneration; animal model; Helicobacter pylori; Helicobacter phylori; H. pylori; 動物モデル; 炎症

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.

大约一半的日本人口感染幽门螺杆菌（H.pylori），除非根除，否则必然会导致慢性胃炎。由于慢性萎缩性胃炎容易导致胃癌（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H.pylori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。由于宿主免疫和炎症反应参与受感染胃上皮细胞的组织再生和分化，并且炎症反应的长期影响可能在致癌过程中发挥作用，因此我们建立了H.pylori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。与此同时，我们还分析了H.pylori感染胃部的局部免疫反应，研究了免疫反应类型与疾病临床表现的相关性。我们发现受感染胃中 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发挥重要作用。此外，我们发现胃中的Th反应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寻找新的生物标志物，从而有助于识别胃癌高危患者。

项目成果

Tomohiro Watanabe, Yoshio Wakatsuki, et al.: "A liver tolerates to a portal antigen by generating CD11c+ cells which select regulatory CD4+ T cells via apoptosis"Hepatology. 38. 403-412 (2003)

Tomohiro Watanabe、Yoshio Wakatsuki 等人：“肝脏通过生成 CD11c 细胞来耐受门静脉抗原，这些细胞通过凋亡选择调节性 CD4 T 细胞”肝病学。

Th response to Helicobacter pylori differs between patients with gastric ulcer and duodenal ulcer

• DOI: 10.1080/00365520510015520
• 发表时间: 2005-06-01
• 期刊: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
• 影响因子: 1.9
• 作者: Itoh, T;Seno, H;Wakatsuki, Y
• 通讯作者: Wakatsuki, Y

Tomohiro Watanabe, Yoshio Wakatsuki, et al.: "Helper CD4+ T cells for IgE response to a dietary antigen develop in the liver"Journal of Allergy and Clinical Immunology. 111. 1375-1385 (2003)

Tomohiro Watanabe、Yoshio Wakatsuki 等人：“肝脏中形成对膳食抗原产生 IgE 反应的辅助 CD4 T 细胞”过敏与临床免疫学杂志。

Tomohiro Watanabe, Yoshio Wakatsuki, et al.: "A liver tolerates to a portal antigen by generating CD11c+ cells which select regulatory CD4+ T cells via apoptosis"Hepatology. (In press). (2003)

Tomohiro Watanabe、Yoshio Wakatsuki 等人：“肝脏通过生成 CD11c 细胞来耐受门静脉抗原，这些细胞通过凋亡选择调节性 CD4 T 细胞”肝病学。

Toshiyuki Itoh, Yoshio Wakatsuki, et al.: "A coordinated cytotoxic effect of IFN-gamma and cross-reactive antibodies in the pathogenesis of Helicobacter pylori gastritis"Helicobacter. 8. 268-278 (2003)

Toshiyuki Itoh、Yoshio Wakatsuki 等人：“IFN-γ 和交叉反应性抗体在幽门螺杆菌胃炎发病机制中的协调细胞毒性作用”