Netrin-1 guides inflammatory cell migration to control mucosal immune responses during intestinal inflammation.
Netrin-1 guides inflammatory cell migration to control mucosal immune responses during intestinal inflammation.
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DOI：
10.4161/tisb.24957
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发表时间：
2013-04-01
期刊：
影响因子：
3.1
通讯作者：
Eltzschig HK
中科院分区：
文献类型：
--
作者：
Aherne CM;Collins CB;Eltzschig HK
肠上皮是一种动态屏障，在肠道内环境稳定和炎症反应中起着积极的作用。炎症性肠病（IBD）期间肠屏障功能失调，上皮细胞通过释放吸引白细胞至肠固有层的信号在产生炎症环境中起重要作用。然而，越来越多的人认识到，肠上皮介导了对驱动分辨率的平衡响应。与神经元发育进行类比，其中化学吸引和化学排斥信号的平衡是定向神经元运动的关键，已经假设这种分泌的线索在白细胞迁移中起作用。Netrin-1是描述最多的神经元导向分子之一，其已被证明在白细胞的定向迁移中起重要作用。在我们的研究之前，netrin-1在IBD中的潜在作用的特征很差。我们将netrin-1定义为肠上皮源性蛋白，其能够限制中性粒细胞募集以减轻急性结肠炎。我们的研究强调，肠上皮细胞在急性炎症期间释放因子，负责微调免疫反应。这些上皮介导的保护机制的探索将阐明健康和疾病中肠上皮屏障的复杂性。
The intestinal epithelium is a dynamic barrier playing an active role in intestinal homeostasis and inflammation. Intestinal barrier function is dysregulated during inflammatory bowel disease (IBD), with epithelial cells playing a significant part in generating an inflammatory milieu through the release of signals that attract leukocytes to the intestinal lamina propria. However, it is increasingly appreciated that the intestinal epithelium mediates a counterbalancing response to drive resolution. Drawing analogies with neuronal development, where the balance of chemoattractive and chemorepellent signals is key to directed neuronal movement it has been postulated that such secreted cues play a role in leukocyte migration. Netrin-1 is one of the best-described neuronal guidance molecules, which has been shown to play a significant role in directed migration of leukocytes. Prior to our study the potential role of netrin-1 in IBD was poorly characterized. We defined netrin-1 as an intestinal epithelial-derived protein capable of limiting neutrophil recruitment to attenuate acute colitis. Our study highlights that the intestinal epithelium releases factors during acute inflammation that are responsible for fine-tuning the immune response. Exploration of these epithelial-mediated protective mechanisms will shed light on the complexity of the intestinal epithelial barrier in health and disease.