Helicobacter pylori Colonization Protects Against Chronic Experimental Colitis by Regulating Th17/Treg Balance
Helicobacter pylori Colonization Protects Against Chronic Experimental Colitis by Regulating Th17/Treg Balance
复制标题
幽门螺杆菌定植通过调节 Th17/Treg 平衡来预防慢性实验性结肠炎。
DOI：
10.1093/ibd/izy107
复制
发表时间：
2018-07-01
影响因子：
4.9
通讯作者：
Wang, Weihong
中科院分区：
文献类型：
--
作者：
Zhang, Hongchen;Dai, Yun;Wang, Weihong
背景
流行病学研究表明，幽门螺杆菌感染与炎症性肠病（IBD）的发病风险呈负相关。探讨了H. pylori感染对IBD的保护作用尚不清楚。本文探讨了胃H. pylori在慢性结肠炎模型上的定植，重点是H. pylori通过调节Th17/Treg免疫应答发挥作用。
方法
慢性结肠炎由葡聚糖硫酸钠（DSS）治疗诱导。进行流式细胞术分析以确定脾脏、肠系膜淋巴结和结肠固有层中的Th17细胞、Treg细胞和M1/M2巨噬细胞。Th17和Treg相关细胞因子的水平通过定量聚合酶链反应测定。H. pylori提取物对巨噬细胞极化状态的影响。
结果
胃H。幽门螺杆菌定植显著改善了DSS诱导的慢性结肠炎的严重程度。H.幽门螺杆菌定植降低了结肠中的Th17细胞和IL-17 A、IL-17 F和IL-21的mRNA水平。同时，H。pylori定植增加Treg细胞和IL-10表达。对于驱动Th17和Treg分化的细胞因子，H. pylori定植增加TGF β，降低IL-6和IL-23。此外，H.幽门螺杆菌定植显著增加结肠中的M2巨噬细胞。在体外，H. pylori提取物促进M2巨噬细胞极化依赖于CagA的存在。
结论
H.幽门螺杆菌定植通过平衡Th17/Treg应答和使巨噬细胞向抗炎M2表型转变来保护免受慢性DSS诱导的结肠炎。我们的研究结果加强了胃H。幽门螺杆菌定植影响结肠的免疫稳态。
Background
Epidemiological studies have demonstrated an inverse association between Helicobacter pylori infection and the risk of developing inflammatory bowel disease (IBD). The mechanisms by which H. pylori infection protects against IBD are unclear. Here, we explored the possible protective effects and mechanisms of gastric H. pylori colonization on a chronic colitis model, with focus on whether H. pylori exerted its effects through regulating Th17/Treg immune responses.
Methods
Chronic colitis was induced by dextran sulfate sodium (DSS) treatment. Flow cytometry analysis was performed to determine Th17 cells, Treg cells, and M1/M2 macrophages in the spleen, mesenteric lymph nodes, and colonic lamina propria. The levels of Th17- and Treg-associated cytokines were measured by quantitative polymerase chain reaction. The direct effect of H. pylori extract on the polarization status of macrophages was determined in vitro.
Results
Gastric H. pylori colonization significantly ameliorated the severity of chronic DSS-induced colitis. H. pylori colonization decreased Th17 cells and mRNA levels of IL-17A, IL-17F, and IL-21 in the colon. Simultaneously, H. pylori colonization increased Treg cells and IL-10 expression. As to cytokines driving Th17 and Treg differentiation, H. pylori colonization increased TGFβ and decreased IL-6 and IL-23. Moreover, H. pylori colonization significantly increased M2 macrophages in the colon. In vitro, H. pylori extract promotion of M2 macrophage polarization was dependent on the presence of CagA.
Conclusions
H. pylori colonization protects against chronic DSS-induced colitis via balancing Th17/Treg responses and shifting macrophages toward anti-inflammatory M2 phenotype. Our results strengthen the rationale for gastric H. pylori colonization affecting the immune homeostasis of the colon.