Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Inflamm Bowel Dis. 2013 Mar-Apr;19(4):720-8. doi: 10.1097/MIB.0b013e3182802a76.
Interleukin 25 (IL-25) is involved in the initiation of T helper cell (Th)2-mediated immunopathologies. In this study, we investigated the expression of IL-25 in inflammatory bowel disease (IBD) and its role in the induction of CD4 T-cell differentiation.
Expression of IL-25 in inflamed mucosa of patients with IBD was determined by quantitative real-time polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. The correlation of IL-25 expression with endoscopic disease activities and C-reactive protein was evaluated. Peripheral blood and lamina propria CD4 T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies in the presence of IL-25. Transcription factors and cytokines were determined with real-time polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay.
IL-25 was significantly decreased in the sera and inflamed mucosa of patients with active IBD compared with controls. It was upregulated in the sera of patients with Crohn's disease after treatment with infliximab. The levels of IL-25 in inflamed mucosa and sera were inversely correlated with endoscopic disease activities and C-reactive protein, respectively, in IBD. IL-25 could markedly inhibit IBD CD4 T cells to produce tumor necrosis factor, interferon γ, and IL-17A but promote IL-10 secretion. It suppressed the differentiation of IBD CD4 T cells into Th1 and Th17 cells but did not interfere with Th2 cell differentiation. Importantly, blockade of IL-10 secretion by IBD CD4 T cells markedly attenuated the inhibitory role of IL-25 in modulating both Th1 and Th17 immune responses.
IL-25 is markedly decreased in IBD and inhibits IBD CD4 T-cell activation and differentiation into Th1/Th17 cells in an IL-10-dependent manner, suggesting that it may be a potential therapeutic agent for IBD.
白细胞介素 25（IL-25）参与 T 辅助细胞（Th）2 介导的免疫病理学。在本研究中，我们研究了白细胞介素 25 在炎症性肠病（IBD）中的表达及其在诱导 CD4 T 细胞分化中的作用。
通过实时定量聚合酶链反应、免疫组织化学和酶联免疫吸附试验测定 IBD 患者炎症黏膜中 IL-25 的表达。评估 IL-25 表达与内镜疾病活动度和 C 反应蛋白的相关性。用抗 CD3 和抗 CD28 单克隆抗体刺激外周血和固有层 CD4 T 细胞，同时存在 IL-25。通过实时聚合酶链反应、流式细胞术和酶联免疫吸附试验测定转录因子和细胞因子。
与对照组相比，活动期 IBD 患者的血清和炎症黏膜中 IL-25 明显降低。在接受英夫利昔单抗治疗后，克罗恩病患者的血清中 IL-25 上调。炎症黏膜和血清中 IL-25 的水平与 IBD 患者的内镜疾病活动度和 C 反应蛋白分别呈负相关。IL-25 可显著抑制 IBD CD4 T 细胞产生肿瘤坏死因子、干扰素 γ 和 IL-17A，但促进 IL-10 分泌。它抑制 IBD CD4 T 细胞向 Th1 和 Th17 细胞分化，但不干扰 Th2 细胞分化。重要的是，IBD CD4 T 细胞 IL-10 分泌的阻断显著减弱了 IL-25 调节 Th1 和 Th17 免疫反应的抑制作用。
IL-25 在 IBD 中明显降低，并以 IL-10 依赖的方式抑制 IBD CD4 T 细胞的激活和向 Th1/Th17 细胞的分化，提示其可能是治疗 IBD 的潜在药物。
