Modeling Celiac Disease: From Pathogenesis to Therapy

Celiac disease (CeD) is a common gastrointestinal disorder triggered by the ingestion of gluten in genetically predisposed individuals. It is characterized by a complex immune response involving both adaptive and innate immunity, ultimately leading to intestinal mucosal damage and a broad range of extraintestinal manifestations. Although great progress has been made in understanding the pathogenesis of CeD, several questions remain unanswered. Furthermore, the only treatment currently available is a gluten-free diet, and research is actively working to find therapies that can at least complement dietary treatment. Understanding the complexity of the mechanisms underlying CeD has required the development and use of different experimental models, which allowed the investigation of specific pathways and cell populations. In this review, we provide a critical and updated overview of the main in vitro, ex vivo, and in vivo models used to investigate CeD-related pathways, including human cell lines, ex vivo culturing of duodenal biopsies, intestinal organoids and mouse models. For each model, we highlight its specific characteristics, advantages and limitations, as well as its potential applications in translational research.