Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway.
Department of Clinical and Molecular Medicine, NTNU, 7030 Trondheim, Norway.
Int J Mol Sci. 2018 Oct 20;19(10):3257. doi: 10.3390/ijms19103257.
The chemokine C-C motif ligand 20 (CCL20) is increased in the colonic mucosa during active inflammatory bowel disease (IBD) and can be found both in the epithelium and immune cells in the lamina propria. The present study investigated CCL20 and C-C motif Chemokine Receptor 6 (CCR6) in peripheral blood mononuclear cells (PBMCs) ( = 40) from IBD patients and healthy controls, to identify inductors of CCL20 release encountered in a local proinflammatory environment. CCL20 release from PBMCs was increased when activating TLR2/1 or NOD2, suggesting that CCL20 is part of a first line response to danger-associated molecular patterns also in immune cells. Overall, ulcerative colitis (UC) had a significantly stronger CCL20 release than Crohn's disease (CD) (+242%, < 0.01), indicating that the CCL20-CCR6 axis may be more involved in UC. The CCL20 receptor CCR6 is essential for the chemotactic function of CCL20. UC with active inflammation had significantly decreased expression and a reduction in CCR6⁺ cells in circulation, indicating chemoattraction of CCR6⁺ cells from circulation towards peripheral tissues. We further examined CCL20 induced release of cytokines from PBMCs. Stimulation with CCL20 combined with TNF increased IL-1β release from PBMCs. By attracting additional immune cells, as well as inducing proinflammatory IL-1β release from immune cells, CCL20 may protract the inflammatory response in ulcerative colitis.
趋化因子 C-C 基序配体 20（CCL20）在活动性炎症性肠病（IBD）期间在结肠黏膜中增加，并且可以在固有层的上皮细胞和免疫细胞中找到。本研究调查了 IBD 患者和健康对照者外周血单个核细胞（PBMC）（= 40）中的 CCL20 和 C-C 基序趋化因子受体 6（CCR6），以鉴定在局部炎症环境中遇到的 CCL20 释放的诱导剂。当激活 TLR2/1 或 NOD2 时，PBMC 释放的 CCL20 增加，表明 CCL20 也是对危险相关分子模式的一线反应的一部分，在免疫细胞中也是如此。总体而言，溃疡性结肠炎（UC）的 CCL20 释放明显强于克罗恩病（CD）（+242%，<0.01），表明 CCL20-CCR6 轴可能更多地参与了 UC。CCL20 受体 CCR6 对于 CCL20 的趋化功能是必需的。活动性炎症的 UC 具有明显降低的表达和循环中 CCR6+细胞的减少，表明 CCR6+细胞从循环向周围组织的趋化吸引。我们进一步检查了 CCL20 诱导的 PBMC 细胞因子释放。用 CCL20 刺激与 TNF 联合使用可增加 PBMC 中 IL-1β 的释放。通过吸引额外的免疫细胞以及诱导免疫细胞中促炎的 IL-1β 释放，CCL20 可能会延长溃疡性结肠炎的炎症反应。
