This commentary describes an innovative air–liquid interface (ALI) duodenal organoid system for studying celiac disease (CeD). Derived from patient biopsies, this model uniquely preserves the native tissue microenvironment, including epithelial, stromal, and diverse tissue-resident immune cells, overcoming the limitations of conventional cultures and animal models. When stimulated with gluten peptides, the organoids replicate key pathological features of CeD, such as epithelial cell death mediated by cytotoxic T cells. Research has identified interleukin-7 (IL-7), secreted by mesenchymal cells, as a critical and previously underappreciated mediator of this gluten-induced autoimmune attack. This discovery highlights IL-7 as a promising therapeutic target and establishes the ALI organoid platform as a powerful tool for investigating complex epithelial–immune interactions in other autoimmune and infectious diseases, drug screening, and personalized medicine.