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小儿炎症性肠病的发病机制。

Mechanisms of Pediatric Inflammatory Bowel Disease.

机构信息

Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease and.

Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114.

出版信息

Annu Rev Immunol. 2016 May 20;34:31-64. doi: 10.1146/annurev-immunol-032414-112151.

Abstract

Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, is characterized by chronic intestinal inflammation due to a complex interaction of genetic determinants, disruption of mucosal barriers, aberrant inflammatory signals, loss of tolerance, and environmental triggers. Importantly, the incidence of pediatric IBD is rising, particularly in children younger than 10 years. In this review, we discuss the clinical presentation of these patients and highlight environmental exposures that may affect disease risk, particularly among people with a background genetic risk. With regard to both children and adults, we review advancements in understanding the intestinal epithelium, the mucosal immune system, and the resident microbiota, describing how dysfunction at any level can lead to diseases like IBD. We conclude with future directions for applying advances in IBD genetics to better understand pathogenesis and develop therapeutics targeting key pathogenic nodes.

摘要

炎症性肠病(IBD),包括克罗恩病和溃疡性结肠炎,其特征是由于遗传决定因素的复杂相互作用、黏膜屏障破坏、异常炎症信号、耐受丧失和环境触发因素导致的慢性肠道炎症。重要的是,儿科 IBD 的发病率正在上升,特别是在 10 岁以下的儿童中。在这篇综述中,我们讨论了这些患者的临床表现,并强调了可能影响疾病风险的环境暴露因素,特别是在具有遗传风险背景的人群中。关于儿童和成人,我们综述了对肠道上皮、黏膜免疫系统和常驻微生物群的理解的进展,描述了任何水平的功能障碍如何导致像 IBD 这样的疾病。最后,我们为将 IBD 遗传学的进展应用于更好地理解发病机制和开发针对关键致病节点的治疗方法提出了未来的方向。

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