Bamias Giorgos, Cominelli Fabio
First Department of Propaedeutic Medicine, Laiko General Hospital, Athens, Greece, and Digestive Health Center of Excellence, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Curr Opin Gastroenterol. 2007 Jul;23(4):365-9. doi: 10.1097/MOG.0b013e3281c55eb2.
According to the current paradigm, ulcerative colitis and Crohn's disease occur in genetically predisposed individuals because of dysregulated immune responses against intraluminal bacterial antigens. Data have recently accumulated supporting alternative hypotheses for the pathogenesis of inflammatory bowel disease. Here, we present novel immunogenetic pathways and discuss their impact on traditional understanding of inflammatory bowel disease.
In the gastrointestinal tract the innate immune system contains intraluminal bacteria locally, avoiding invasion of the deeper layers and preventing induction of long-standing proinflammatory responses. Failure of this protective function of the innate immune system appears to be the primary defect in inflammatory bowel disease, as a result of impairment of NOD2 signaling or other unidentified deficiencies. The adaptive immune response that ensues was thought to be strictly differentiated between T-helper-1 mediated in Crohn's disease and T-helper-2 mediated in ulcerative colitis. This concept is rapidly changing, however, in light of recent evidence suggesting that tissue injury in inflammatory bowel disease is mediated by novel effector pathways, the most prominent of which is the interleukin-23/Th17 axis.
Elucidation of the pathways that underlie chronic intestinal inflammation will facilitate the development of new treatments with increased specificity and probably with decreased toxicity.
根据当前范式，溃疡性结肠炎和克罗恩病发生于具有遗传易感性的个体，是由于针对肠腔内细菌抗原的免疫反应失调。最近积累的数据支持了炎症性肠病发病机制的其他假说。在此，我们介绍新的免疫遗传途径，并讨论它们对炎症性肠病传统认识的影响。
在胃肠道中，固有免疫系统在局部容纳肠腔内细菌，避免其侵入更深层并防止引发长期的促炎反应。固有免疫系统的这种保护功能失效似乎是炎症性肠病的主要缺陷，这是由于NOD2信号传导受损或其他不明缺陷所致。随后的适应性免疫反应曾被认为在克罗恩病中由辅助性T细胞1介导，在溃疡性结肠炎中由辅助性T细胞2介导。然而，鉴于最近的证据表明炎症性肠病中的组织损伤由新的效应途径介导，其中最突出的是白细胞介素-23/辅助性T细胞17轴，这一概念正在迅速改变。
阐明慢性肠道炎症的潜在途径将有助于开发特异性更高且可能毒性更低的新疗法。
