INSERM, UMR989, Université Paris Descartes, Sorbonne Paris Cité, Hôpital Necker-Enfants Malades, Assistance-Publique-Hopitaux de Paris, Paediatric Gastroenterology Unit, Paris, France.
Inflamm Bowel Dis. 2012 Jul;18(7):1260-6. doi: 10.1002/ibd.21905. Epub 2011 Oct 12.
Interleukin (IL)-23, IL-17A, IL-17F, and interferon-gamma (IFN-γ) are important mediators of inflammatory colitis and are potential therapeutic targets in inflammatory bowel disease (IBD). Their expression profile in the different parts of normal noninflammatory intestine is unclear and their changes during pathology have not yet been addressed in pediatric IBD patients.
We quantified the transcriptional expression of IL-23, IL-12, IL-17A, IL-17F, IL-6, and IL-10 in healthy, noninflammatory duodenum, ileum, and colon and in inflamed and noninflamed biopsies of pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC).
In healthy tissue, expression of IL-17A is highest in the ileum, with IFN-γ expression lowest in the colon. Compared to healthy sections, CD patients displayed increased IL-12p35 and IFN-γ levels in noninflamed ileum and colon, respectively. Modifications of cytokine expression between noninflamed and inflamed tissues was characterized by increased IL-17A in UC colon, IFN-γ in CD colon, and IL-17A, IFN-γ and IL-6 in CD ileum. Elevated IL-17A levels were positively correlated with IFN-γ in both inflammatory CD and UC but IL-17A and IFN-γ were correlated with IL-23p19 in CD ileum only.
The expression of Th1 and Th17 cytokines varies along the intestine, indicating local specific regulation mechanisms. However, the cytokine expression patterns in the same tissue depends on the pathology, with a Th1 or a Th17 profile in the colon of CD and UC patients, respectively, and a Th1/Th17 profile in the ileum of CD patients. This indicates overlapping but distinct immune mechanisms driving intestinal inflammation in these two pathologies.
白细胞介素（IL）-23、IL-17A、IL-17F 和干扰素-γ（IFN-γ）是炎症性结肠炎的重要介质，也是炎症性肠病（IBD）的潜在治疗靶点。它们在正常非炎症性肠道的不同部位的表达谱尚不清楚，其在儿科 IBD 患者中的病理变化尚未得到解决。
我们定量检测了健康、非炎症性十二指肠、回肠和结肠以及克罗恩病（CD）和溃疡性结肠炎（UC）患儿的炎症和非炎症活检组织中 IL-23、IL-12、IL-17A、IL-17F、IL-6 和 IL-10 的转录表达。
在健康组织中，IL-17A 在回肠中的表达最高，而 IFN-γ 在结肠中的表达最低。与健康组织相比，CD 患者的非炎症性回肠和结肠中分别显示出 IL-12p35 和 IFN-γ 水平增加。非炎症组织和炎症组织之间细胞因子表达的变化特征是 UC 结肠中 IL-17A 增加，CD 结肠中 IFN-γ 增加，CD 回肠中 IL-17A、IFN-γ 和 IL-6 增加。CD 中炎症和非炎症组织中升高的 IL-17A 水平与 IFN-γ 呈正相关，但仅在 CD 回肠中，IL-17A 和 IFN-γ 与 IL-23p19 相关。
Th1 和 Th17 细胞因子的表达沿肠道变化，表明存在局部特定的调节机制。然而，同一组织中的细胞因子表达模式取决于病理学，CD 和 UC 患者的结肠呈 Th1 或 Th17 表型，CD 患者的回肠呈 Th1/Th17 表型。这表明在这两种疾病中，有重叠但不同的免疫机制驱动肠道炎症。
