Department of Tumor Genetics and Immunogenetics, Max Delbrück Center for Molecular Medicine (MDC), Berlin, 13125, Germany.
J Mol Med (Berl). 2010 Nov;88(11):1169-80. doi: 10.1007/s00109-010-0658-6. Epub 2010 Aug 27.
Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune and infectious diseases, such as rheumatoid arthritis, Sjögren's syndrome, and Helicobacter pylori-induced gastritis. Homeostatic chemokines are considered to be involved in the formation of such tertiary lymphoid tissue. High expression of CXCL13 and its receptor, CXCR5, has been associated with the formation of ectopic lymphoid follicles in chronic infectious diseases. Here, we defined the role of CXCR5 in the development of mucosal tertiary lymphoid tissue and gastric inflammation in a mouse model of chronic H. pylori infection. CXCR5-deficient mice failed to develop organized gastric lymphoid follicles despite similar bacterial colonization density as infected wild-type mice. CXCR5 deficiency altered Th17 responses but not Th1-type cellular immune responses to H. pylori infection. Furthermore, CXCR5-deficient mice exhibited lower H. pylori-specific serum IgG and IgA levels and an overall decrease in chronic gastric immune responses. In conclusion, the development of mucosal tertiary ectopic follicles during chronic H. pylori infection is strongly dependent on the CXCL13/CXCR5 signaling axis, and lack of de novo lymphoid tissue formation attenuates chronic immune responses.
异位淋巴滤泡是慢性炎症性自身免疫和感染性疾病（如类风湿关节炎、干燥综合征和幽门螺杆菌引起的胃炎）的一个关键特征。稳态趋化因子被认为参与了这种三级淋巴组织的形成。CXCL13 及其受体 CXCR5 的高表达与慢性传染病中异位淋巴滤泡的形成有关。在这里，我们在慢性 H. pylori 感染的小鼠模型中定义了 CXCR5 在黏膜三级淋巴组织和胃炎症发展中的作用。尽管感染野生型小鼠的细菌定植密度相似，但 CXCR5 缺陷型小鼠未能形成有组织的胃淋巴滤泡。CXCR5 缺陷改变了 Th17 反应，但对 H. pylori 感染的 Th1 型细胞免疫反应没有影响。此外，CXCR5 缺陷型小鼠表现出较低的 H. pylori 特异性血清 IgG 和 IgA 水平以及慢性胃免疫反应的总体下降。总之，在慢性 H. pylori 感染期间黏膜三级异位滤泡的发展强烈依赖于 CXCL13/CXCR5 信号轴，而新的淋巴组织形成的缺乏会减弱慢性免疫反应。
