Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases

被引:340
作者
Fasano, A
Shea-Donohue, T
机构
[1] Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Ctr Celiac Res, Baltimore, MD 21201 USA
来源
NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY | 2005年 / 2卷 / 09期
关键词
autoimmune; innate immunity; intestinal permeability; tight junction; toll-like receptor;
D O I
10.1038/ncpgasthep0259
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and electrolytes, and to water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to nonself-antigens. When the finely tuned trafficking of macromolecules is dysregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of autoimmunity, which are based on molecular mimicry and/or the bystander effect, and suggests that the autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing intestinal barrier function. Understanding the role of the intestinal barrier in the pathogenesis of gastrointestinal disease is an area of translational research that encompasses many fields and is currently receiving a great deal of attention. This review is timely given the increased interest in the role of a 'leaky gut' in the pathogenesis of gastrointestinal diseases and the advent of novel treatment strategies, such as the use of probiotics.
引用
收藏
页码:416 / 422
页数:7
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