Exosomes orchestrate celiac disease pathogenesis by presenting deamidated gliadin and dysregulating miRNAs

Celiac disease (CD) is a T-cell-mediated enteropathy triggered by gluten ingestion, characterized by a profound breakdown of mucosal tolerance. Current understanding highlights complex genetic, immunologic, and environmental factors, but the precise spatial processes of intercellular communication across the epithelial-lamina propria barrier remain poorly understood. This gap in knowledge limits the development of advanced diagnostics and targeted therapies beyond a strict gluten-free diet. Exosomes, once considered passive by-products, are now recognized as critical mediators in this autoinflammatory cascade.

This review critically discusses the dual role of exosomes in Celiac disease pathogenesis, synthesizing current understanding of their function as both pathogenic propagation vectors and potential real-time liquid biopsies. It explores how exosomes mediate intercellular communication across the epithelial-lamina propria barrier and their impact on immune responses. The authors examine the mechanisms by which exosomes contribute to disease progression and their emerging utility in diagnostic and therapeutic strategies for CD.

Exosomes functionally mediate the non-canonical presentation of deamidated gliadin peptides and disease-associated HLA-DQ complexes. This direct presentation primes pathogenic CD4+ T cells independently of conventional cellular synaptic interaction, a significant finding in CD immunology. Simultaneously, dysregulated exosomal microRNA (miRNA) signatures were found to undermine tight junction integrity, a crucial barrier function. These miRNA changes also promote systemic pro-inflammatory signaling loops, providing a probable mechanistic link to the often-observed extra-intestinal symptoms of CD. The review highlights the potential of exosomes as non-invasive, real-time liquid biopsies for diagnosis and monitoring.

Exosomes functionally mediate the non-canonical presentation of deamidated gliadin peptides and disease-associated HLA-DQ complexes, directly priming pathogenic CD4+ T cells.