Background

Crohn’s disease (CD) and ulcerative colitis (UC), the two main entities of inflammatory bowel disease (IBD), are characterised by chronic and relapsing/remitting inflammation of the gastrointestinal tract, and occasionally ultimately result in debilitating intestinal fibrosis. Apart from their key role in fibrosis, there is evidence that subepithelial myofibroblasts (SEMFs) participate in the IBD inflammatory cascade, as they express various pro-inflammatory cytokine receptors. We examined the effect of pro-inflammatory IL-17—the hallmark cytokine of T-lymphocytes differentiated to Th17—on the expression of lymphocyte-chemotactic chemokines in SEMFs.

Methods

SEMFs were isolated from endoscopically obtained colonic biopsies from healthy controls, set to culture and stimulated with 100 ng/ml IL-17 for 6 h. Total RNA was extracted and mRNA expression of CCL5, CXCL1 and CXCL11 was assessed with reverse transcription quantitative (RT-q) PCR. Changes in cytokine mRNA are provided as medians (IQR).

Results

Untreated SEMFs had a basal expression of chemokines of the CCL and CXCL family groups. So far, our study has shown that the IL-17 stimulation leads to a statistically significant upregulation of CCL and CXCL chemokines in SEMFs (p < 0.001). In detail, CCL5 was upregulated 5.7-fold (4.9–7.5), CXCL1 72.9-fold (63.1–90.7) and CXCL11 25.4-fold (17.3–37.3).

Conclusion

IL-17 induced the expression of chemotactic factors in SEMFs. Our results further support a potential role of SEMFs in the shaping of intestinal mucosal immunity by serving as immunological intermediates that respond to cytokines of adaptive immunity and amplify the recruitment of immune cells via chemokine production.

中文翻译：

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P057 IL-17调节人结肠上皮下成纤维细胞中趋化趋化因子的表达

背景

克罗恩病（CD）和溃疡性结肠炎（UC）是炎症性肠病（IBD）的两个主要实体，其特征是胃肠道的慢性炎症和复发性/缓解性炎症，有时最终会导致肠道纤维化。除了它们在纤维化中的关键作用外，有证据表明上皮下肌成纤维细胞（SEMF）参与IBD炎症级联反应，因为它们表达各种促炎性细胞因子受体。我们检查了促炎性IL-17（分化为Th17的T淋巴细胞的标志性细胞因子）对SEMF中淋巴细胞趋化趋化因子表达的影响。

方法

从健康对照的内窥镜下获得的结肠活检物中分离SEMF，进行培养并用100 ng / ml IL-17刺激6小时。提取总RNA，并通过逆转录定量（RT-q）PCR评估CCL5，CXCL1和CXCL11的mRNA表达。细胞因子mRNA的变化以中位数（IQR）的形式提供。

结果

未经处理的SEMF具有CCL和CXCL家族组趋化因子的基础表达。到目前为止，我们的研究表明，IL-17刺激导致SEMF中CCL和CXCL趋化因子的统计学上显着上调（p <0.001）。详细而言，CCL5上调了5.7倍（4.9-7.5），CXCL1 72.9倍（63.1-90.7）和CXCL11 25.4倍（17.3-37.3）。

结论

IL-17诱导SEMFs中趋化因子的表达。我们的研究结果进一步证明了SEMFs通过对免疫适应性细胞因子产生反应并通过趋化因子产生放大免疫细胞募集作用的免疫学中间体，在肠道粘膜免疫形成中发挥潜在作用。