In vitromodels for gluten toxicity: relevance for celiac disease pathogenesis and development of novel treatment options

Abstract

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.

Identification of Autophagy-Related Genes and Their Regulatory miRNAs Associated with Celiac Disease in Children

“…Lastly, the in vitro results using the Caco-2 cell model, widely adopted in CD studies [58,59] and challenged with a direct digested gliadin administration, provided a possible mechanistic view of the regulatory effects of miRNAs, specifically miR-17, on the expression of a key autophagic gene as ATG7 . Similar to our previous results [29], we showed that even only modulating intracellular miR-17 levels, this can significantly alter the autophagic status of the cells.…”

A Silent or Hypo-symptomatic Disease Can Erupt: Acute Presentations of Celiac Disease

“…Ex-vivo gluten application on gluten-free diet intestinal biopsy, bypass the obstacle. Many ex-vivo, in vitro models were described, using human originated intestinal cell-lines or CD patients small bowel mucosal biopsies [41,42]. We know nowadays that gluten or gliadin, when incubated with primary cultures of CD patients on glutenfree diet,induces morphological as well as immunological aberrations.…”

Despite sequence homologies to gluten, salivary proline-rich proteins do not elicit immune responses central to the pathogenesis of celiac disease

“…To detect the antigenic properties of gliadin peptides, in vitro challenge of CD patients' PBMCs (55), small intestinal biopsies (31), and gluten-specific T cell lines generated from biopsies (35,38) have been employed. In our study we employed PBMCs.…”