Pediatric Research Center, University of Tampere and Tampere University Hospital, Tampere, Finland.
Exp Biol Med (Maywood). 2012 Feb;237(2):119-25. doi: 10.1258/ebm.2011.011294. Epub 2012 Jan 26.
In genetically predisposed individuals, dietary gluten in wheat, rye and barley triggers celiac disease, a systemic autoimmune disorder hallmarked by an extensive small-bowel mucosal immune response. The current conception of celiac disease pathogenesis is that it involves components of both innate and adaptive immunity whose activation typically leads to small-bowel villous atrophy with crypt hyperplasia. Currently, the only effective treatment for celiac disease is a strict lifelong gluten-free diet excluding all wheat-, rye- and barley-containing food products. During the diet, the clinical symptoms improve and the small-bowel mucosal damage recovers, while re-introduction of gluten into the diet leads to re-appearance of the symptoms and deterioration of the small-bowel mucosal architecture. In view of the restricted nature of the diet, alternative treatment is warranted. Improved understanding of the molecular basis of celiac disease has enabled researchers to suggest other therapeutic approaches. Although there is no animal model reproducing all features of celiac disease, the use of in vitro approaches including a variety of cell lines and the celiac patient small-bowel mucosal biopsy organ culture has generated knowledge about pathogenesis of celiac disease. In these culture systems, gluten induces different effects that can be quantified, thus also enabling studies concerning the efficacy of candidate therapeutic compounds for celiac disease. This review describes the intestinal epithelial cell models, celiac patient T-cell lines and clones, as well as the small-bowel mucosal organ culture methods widely used in studies of celiac disease, and summarizes the major findings obtained with these systems.
在遗传易感性个体中，小麦、黑麦和大麦中的膳食 gluten 会引发乳糜泻，这是一种全身性自身免疫性疾病，其特征是广泛的小肠黏膜免疫反应。目前对乳糜泻发病机制的认识是，它涉及先天和适应性免疫的成分，其激活通常导致小肠绒毛萎缩伴隐窝增生。目前，乳糜泻的唯一有效治疗方法是严格的终生无麸质饮食，排除所有含小麦、黑麦和大麦的食品。在饮食期间，临床症状改善，小肠黏膜损伤恢复，而重新引入 gluten 会导致症状再次出现和小肠黏膜结构恶化。鉴于饮食的限制性质，需要替代治疗。对乳糜泻分子基础的深入了解使研究人员能够提出其他治疗方法。尽管没有能够复制乳糜泻所有特征的动物模型，但体外方法的应用，包括各种细胞系和乳糜泻患者小肠黏膜活检器官培养，已经产生了关于乳糜泻发病机制的知识。在这些培养系统中，gluten 会引起不同的可量化的影响，从而也能够研究乳糜泻候选治疗化合物的疗效。这篇综述描述了广泛用于乳糜泻研究的肠上皮细胞模型、乳糜泻患者 T 细胞系和克隆，以及小肠黏膜器官培养方法，并总结了这些系统获得的主要发现。
