Exosomes in celiac disease: From pathogenesis to diagnostic and therapeutic potential

Celiac disease (CD) is a prototypical example of gluten-induced enteropathy characterized by a strong breakdown of mucosal tolerance. However, the spatial processes underlying intercellular communication across the epithelial-lamina propria barrier remain poorly known. Exosomes have evolved to be useful orchestrators of this autoinflammatory cascade. In contrast to their passive metabolic by-product role, gut-derived exosomes functionally mediate the non-canonical presentation of deamidated gliadin peptides and disease-associated HLA-DQ complexes, which directly prime pathogenic CD4⁺ T cells independently of conventional cellular synaptic interaction. At the same time, dysregulated exosomal microRNA (miRNA) signatures undermine tight junction integrity and promote pro-inflammatory signaling loops systemically, providing a probable mechanistic link to extra-intestinal symptoms. In this review, the dual role of exosomes as pathogenic propagation vectors and real-time liquid biopsies in CD will be critically discussed.