Mucosal Biology Research Center and Center for Celiac Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Clin Gastroenterol Hepatol. 2012 Oct;10(10):1096-100. doi: 10.1016/j.cgh.2012.08.012. Epub 2012 Aug 16.
One of the most important and overlooked functions of the gastrointestinal tract is to provide a dynamic barrier to tightly controlled antigen trafficking through both the transcellular and paracellular pathways. Intercellular tight junctions (TJ) are the key structures regulating paracellular trafficking of macromolecules. Although steady progress has been made in understanding TJ ultrastructure, relatively little is known about their pathophysiological regulation. Our discovery of zonulin, the only known physiological modulator of intercellular TJ described so far, increased understanding of the intricate mechanisms that regulate gut permeability and led us to appreciate that its up-regulation in genetically susceptible individuals may lead to immune-mediated diseases. This information has translational implications, because the zonulin pathway is currently exploited to develop both diagnostic and therapeutic applications pertinent to a variety of immune-mediated diseases.
胃肠道最重要且常被忽视的功能之一是通过细胞内和细胞旁途径为严格控制的抗原转运提供动态屏障。细胞间紧密连接（TJ）是调节大分子细胞旁转运的关键结构。尽管在理解 TJ 超微结构方面已经取得了相当大的进展，但对于其病理生理学调节却知之甚少。我们发现了zonulin，这是迄今为止唯一已知的细胞间 TJ 的生理性调节剂，这增加了对调节肠道通透性的复杂机制的理解，并使我们认识到其在遗传易感个体中的上调可能导致免疫介导的疾病。这些信息具有转化意义，因为 zonulin 途径目前被用于开发与多种免疫介导疾病相关的诊断和治疗应用。
