In Situ Gluten–Chitosan Interlocked Self‐Assembled Supramolecular Architecture Reduces T‐Cell‐Mediated Immune Response to Gluten in Celiac Disease

SCOPE: The prevalence of celiac disease has increased since the last half of the 20th century and is now about 1% in most western populations. At present, people who suffer from celiac disease have to follow a gluten-exclusion diet throughout their lives. Compliance to this restrictive diet is demanding and the development of alternative strategies has become urgent. METHODS AND RESULTS: In this context, it is found that the biocompatible aminopolysaccharide chitosan imposes a different gluten reorganization after gluten redox reaction producing in situ mechanically interlocked supramolecular assemblies between gluten and chitosan. These new structures result in the decrease of gluten digestibility, tissue transglutaminase deamidation activity, and interferon-γ production in intestinal T cell lines generated from biopsy specimens of celiac disease patients. CONCLUSION: Overall, the results demonstrate the potential of this research avenue to celiac disease is problematic, as the reorganization of gluten proteins to a novel supramolecular architecture shows a positive impact on known pathogenesis mechanisms of the disease. At present, the only therapy for celiac disease is adherence to a gluten-free diet. Here, it is shown that chitosan-imposed gluten reorganization to an interlocked self-assembled supramolecular architecture reduces gluten digestibility, R5-reactivity, tissue transglutaminase deamidation activity, and its capacity to stimulate a T-cell-mediated immune response in celiac disease.